The aim of this study was to examine the relationship between PM2.5 daily air concentrations and pediatric emergency department (ED) visits for respiratory diseases in a Greek suburban area. All pediatric ED visits for asthma-, pneumonia- and upper respiratory infection (URI)-related complaints were recorded during the one-year period. The 24-h PM2.5 air pollution data were prospectively collected from twelve fully automated air quality monitoring stations. The mean annual concentration of PM2.5 was 30.03 μg/m3  Air Quality Guidelines (AQG) Annual mean concentration: 10 μg/m3). PM2.5 levels rose above the WHO Air Quality Guidelines (AQG) 24-h concentrations (25 μg/m3)), 178 times (48.6% of the study period). When PM2.5 levels were above the daily limit, an increase of 32.44% (p < 0.001) was observed in daily pediatric ED visits for respiratory diseases and the increase was much higher during spring . A 32% (p < 0.001) increase was observed in URI-related visits, when PM2.5 levels were ≥25 μg/m3, compared to the mean daily visits when PM2.5 levels were <25 μg/m3. Air pollution levels were associated with increased pediatric ED visits for respiratory-related diseases. Ambient air pollution accounts for an estimated 4.2 million deaths worldwide. Particulate matter (PM) PM2.5 levels were found to be higher in winter when compared with spring , summer  and autumn .2.5 in the city of Volos was 30.03 (17.47) μg/m3 (WHO yearly limit: 10 μg/m3). As presented in 2.5 levels rose above 25 μg/m3, the daily limit suggested by WHO, 178 times (48.6% of the study period). When PM2.5 levels were above the daily limit, an increase of 32.44%  was observed in daily pediatric ED visits for respiratory diseases. 2.5 levels of the previous day raised above 25 μg/m3 (p < 0.001). When further analysis was performed based on the season  (p: <0.001), summer  and autumn .Regarding URI-related visits, a statistically significant increase was observed when PM <0.001) ; the inc <0.001) . The num2.5 levels were ≥25 μg/m3, compared to the mean daily visits when PM2.5 levels were <25 μg/m3  (r Square = 0.103) with the total number of ED visits. This correlation is described by the following equation: total number of ED visits = 8.546 + 0.104 × PM2.5 levels , asthma exacerbations (19.23%) and pneumonia (46.24%), when PM2.5 levels exceeded the proposed daily limit of 25 μg/m3, although not statistically significant for asthma and pneumonia.Our study demonstrated that high PM2.5 levels in the city of Volos exceeded the proposed daily limit set by the air quality guidelines issued by WHO for 48.6% of the study period. The proposed mean annual limit was also exceeded. The highest PM2.5 levels were noted during winter and spring. Our findings are in accordance with a previous study set in the city of Volos by Moustris et al. [PMs et al. . The res2.5 pollution [The same trend has been noted in several urban centers worldwide ,20, withollution . In addiollution . In Euroollution , includiollution ,24. TherSince fine particulate matter pollution is mainly anthropogenic in nature, it is no wonder that urban centers are more severely affected . More sp2.5 [Financial crises have also been shown to lead to increased emissions of pathogenic air pollutants, especially PM2.5 . This ma2.5 , which h2.5 .2.5 levels, proper measures need to be taken, enabling the reduction of coal-based fuel usage and industrial fine particulate matter generation [2.5 emissions in urban centers, in order to ameliorate the harmful effects of air pollution on human health.In order to mitigate the effects of fine particulate matter on human health, environmental monitoring and evaluation, as well as strict environmental law enforcement, are necessary . In an aneration . By implneration . The str2.5 can have various detrimental health effects [2.5 allows the particles to reach the small alveoli [2.5 may irritate or damage the alveolar wall and instigate lung dysfunction [2.5 pollution have been associated with a variety of acute and chronic respiratory diseases [It has been previously established that high levels of PM effects . The sma alveoli . Subsequfunction . As a rediseases . Moreovediseases ,34. 2.5 levels raised higher than the proposed limit. The association between the short-term increase in PM2.5 levels and the incidence of several acute diseases has been previously established in both adult and pediatric patients, as ED visits, especially for respiratory causes, have been shown to significantly increase for three days following excess fine particulate matter pollution [2.5 levels, utilizing the equation “Total number of ED visits = 8.546 + 0.104 × PM2.5 levels”.Our results corroborate the above findings since the number of pediatric ED visits in the city of Volos increased as much as 32.44% in the days that PMollution ,36. In aollution . Moreove2.5, owing to their immature immune system and narrower airways [2.5 levels exceeded the daily proposed limit, suggesting that air pollution severely affects the risk of developing respiratory infections in children.The harmful effect of fine particulate matter on the respiratory system seems to be multifactorial and possibly includes immune response modification and inflammation  and redu airways . Indeed, airways ,42. Simi2.5 levels were associated with an increase in pediatric ED visits for asthma-like symptoms, reaching an increase of 19.23%, although not statistically significant. These findings are consistent with the existing literature, showcasing that children are more likely than adults to exhibit asthma-like symptoms during periods of short-term exposure to high PM2.5 concentrations and are at an increased risk for hospitalization [There is growing evidence that fine particulate matter pollution is a major instigator of asthma exacerbations ,44. Airblization .2.5 levels exceed the proposed safety limit [While the effect of fine particulate matter exposure to the development of respiratory symptoms has already been established, environmental health awareness and preparedness is not common amongst physicians . For thity limit . http://greenyourair.org/link (accessed on 9 June 2021)) that show real-time measurements of PM2.5 levels, in order to limit their activities accordingly. It is also crucial for physicians to be vigilant during periods of high levels of fine particulate matter pollution and accurately inform and monitor their patients, especially those who are highly susceptible to the harmful effects of air pollution, like children suffering from asthma [2.5 pollution, in order to effectively optimize patient care. As previously mentioned, it is possible to use mathematical equations in order to estimate the number of ED visits based on the PM2.5 levels of the day. Using those equations, emergency physicians could anticipate the greater influx of patients which may present in the ED during days of high atmospheric pollution, in order to efficiently organize the ED personnel and resources, thus greatly improving patient management. However, it is important to highlight that the number of ED visits is also affected by several other reasons, such as season and viral outbreaks. While environmental medicine can be utilized in order to optimize ED patient care, a variety of factors have to be taken into consideration when managing ED resources and personnel.Individuals can be informed on the daily levels of air pollution through specially created websites, similar to the GreenYourAir website in Volos (m asthma . Further2.5 levels, thus not accurately reflecting the individual exposure of our study participants. Furthermore, as the diagnoses were performed in an emergency setting, it is possible that some of them were inaccurate, leading to misclassification. Our study has certain limitations that should be acknowledged. Firstly, our analysis implemented the mean values of the measured PM2.5 in the city of Volos was 30.03 μg/m3, much higher than the WHO yearly limit of 10 μg/m3. When PM2.5 levels were above the daily limit, an increase of 32.44% was observed in daily pediatric ED visits for respiratory-related conditions, such as asthma, pneumonia and URI, with the increase being higher during winter and spring. The mean annual concentration of PMLocal data from different cities-environments across Greece will improve our understanding of air pollution on the health of children and will aid policymakers in decisions that relate to the sustainability of development and prevention of air pollution. A global prevention policy should be designed in order to combat anthropogenic air pollution as a complement to the correct handling of the adverse health effects associated with air pollution. International cooperation in terms of research, development, administration policy, monitoring, and politics is vital for effective pollution control. These challenges need to be addressed if we are to protect the health of children in the coming generations.


BackgroundIn recent years, there is an increase in the proportion of the elderly population in the world. With an increase in patients' age, there is a change in the comorbidities and causes for Intensive care unit (ICU) admissions. More studies are needed to redefine healthcare delivery to elderly patients admitted to ICU.AimsThe aims are to assess the disease pattern and outcome in elderly patients admitted to the Medical ICU and to determine factors affecting the outcomes in elderly patients admitted to the Medical ICU.MethodsThis was a retrospective cross-sectional study conducted in the Medical ICU of a tertiary care hospital for six months. Patients who met inclusion and exclusion criteria were included in this study. Data collected from medical records were statistically analysed.ResultsOut of 859 newly admitted patients to the Medical ICU, 196 (22.81%) were elderly patients (age > 60 years). The mean age of elderly patients was 69.8 ± 7.65 years. The mortality rate in elderly patients aged > 60 years was 36.70%, which was higher when compared to 23.60% in patients aged ≤ 60 years, and the correlation was statistically significant (p<0.0001). Neurological disorders (42.8%) were the most common cause of admissions, followed by renal disorders (13.26%), respiratory diseases (9.7%), and infections (9.18%). Deaths due to neurological disorders were most common (43.66%) followed by renal disorders (14.08%), infections (11.26%), and respiratory diseases (7%). The mean number of comorbidities in elderly patients was 1.99 ± 1.21. The mortality rate in elderly patients with more than three comorbidities was 56.52%, which was higher when compared to 33.52% in elderly patients with comorbidities ≤3, and the correlation was statistically insignificant (p=0.1275). The mean length of ICU stay in elderly patients was 9.14 ± 6.73 days. The length of stay in ICU was prolonged in patients with more number of comorbidities, which was statistically significant (p<0.0001). The mortality rate was higher in patients with prolonged length of stay, and the correlation was statistically significant (p=0.0013).ConclusionThe insight over the proportion of older patients admitted to the ICU will enable policy-makers to plan accordingly. Mortality in elderly patients was high. Hence there is a need to redefine healthcare delivery to elderly patients in terms of triage and level of care in ICU. For better outcomes, risk categorisation can be done based on the number of comorbidities for optimal care. Exclusive geriatric intensive care units were needed for better care of elderly patients. In recent years there is an increase in the proportion of the elderly population in the world. In India, forecasts predict the percentage of the population older than 60 years will increase from 8% in 2015 to 19% in 2050 [There is a longer prehospital delay for elderly acute myocardial infarction patients when compared to the young . Age-basWith an increase in patients' age, there is a change in the comorbidities and causes for Intensive care unit admissions. Old age is recognised as a crucial independent risk factor for death . Apart fIn India, ageing of the population warrants an up-gradation of hospitals to provide optimal ICU care for elderly patients. Only a few Indian studies researched this issue. Thangam et al. conducted a study to determine the factors associated with the outcome of older patients admitted to the Geriatric ICU of a south Indian hospital . ThangamIn view of the above context, the present study attempts to explore the disease patterns, outcomes, and factors affecting the outcome in elderly patients admitted to the Medical ICU of a large tertiary care hospital. Aims and objectivesThe main aims and objectives are to assess the disease pattern and outcome in elderly patients admitted to the Medical ICU and to determine factors affecting the outcomes in elderly patients admitted to the Medical ICU.Study design and populationThis was a retrospective cross-sectional study conducted in the Medical ICU at Sri Venkateswara Ramnarain Ruia Government General Hospital (SVRRGGH), Tirupati, for a period of six months from September 2011 to March 2012.Inclusion criteriaPatients aged >60 years with medical illness admitted for the first time to the Medical ICU were included in this study.Exclusion criteriaElderly patients with surgical/trauma-related illnesses and those who have incomplete medical records were excluded from this study.MethodologyPatients who met the inclusion and exclusion criteria were included in this study. This study was conducted with prior permission and ethical clearance from concerned authorities. The demographic variables: age, gender, and address; and clinical variables: comorbidities, diagnosis, length of stay, and outcome were collected from medical records. Comorbidities like diabetes mellitus, hypertension, dyslipidaemia, immunocompromised status, cardiovascular disease, cerebrovascular disease, malignancy, and chronic kidney disease were noted.Admissions, age distribution, gender distribution, the number of comorbidities, and length of stay in ICU were assessed. From the diagnosis, the primary system that was a reason for hospitalisation was identified. The outcome was measured either as discharged or deceased. Collected data were interpreted by descriptive analysis using IBM SPSS Statistical software for Windows, Version 21.0 . Descriptive statistics (mean±standard deviation or count/proportion) were calculated for each characteristic. The Pearson correlation test was applied to investigate relationships between the outcome and other characteristics such as age groups , gender, number of comorbidities, the primary system involved, and duration of stay. A p-value of <0.05 was considered to be statistically significant.Age and outcomeA total of 859 patients of all age groups were newly admitted to Medical ICU. Out of 859 patients, 196 (22.81%) were elderly patients (age > 60 years), and 663 (77.18%) patients were aged ≤60 years. Among elderly patients, 115 (58.67 %) belong to the 61-70 age group,62 (31.63%) belong to the 71-80 age group and 19 (11.73 %) belong to the 81-90 age group . The mortality rate in patients aged ≤60 years was 23.6% (157). The mortality rate in elderly patients with age > 60 years was 36.7% (71). We noticed a statistically significant association between outcomes of ≤60-year-old patients and >60-year-old patients with a p-value<0.0001 , (71-80), and (81-90) were 33.04% (38), 38.70% (24), and 47.36% (9), respectively. There was no statistically significant correlation between age group and outcome (p=0.4293)  were male, and 77 (39.20%) were female. Out of 71 deaths in elderly patients, 44 were male and 27 were female. The mortality rates among elderly male and female patients were 36.97% and 35.07%. We found no association between gender and outcome with a p-value of 0.7858, which was statistically insignificant  cases got admitted with neurological disorders. Neurological disorders were followed by renal disorders, respiratory diseases, and infections, which account for 26 13.26%), 22 (9.70%), and 18 (9.18%) cases, respectively  was the most common cause of admissions (27.5%) in elderly patients. Meningitis (11.73%), chronic kidney disease (9.18%), were leading causes of admissions followed by CVA.Deaths due to neurological disorders accounted for 43.66% of total deaths. Deaths due to renal disorders, infections, and respiratory disorders were 14.08%,11.26%, and 7%, respectively. There was no statistically significant association between the primary system involved and the outcome (p=0.7255) , chronic kidney disease 9.85%), heart failure (9.85%), and cerebral malaria (8.45%) were leading causes of death after CVA. There was no statistically significant correlation between the final diagnosis and outcome   Table .Length of stay and comorbiditiesThe mean length of stay in the Medical ICU by elderly patients was 9.14 ± 6.73 days. The length of stay was prolonged in patients with three or more comorbidities when compared with patients with one or two comorbidities. The association between comorbidities and length of stay was statistically significant, with a p-value<0.0001 Table .Length of stay and outcomeWhen the duration of stay in ICU was correlated to the outcome, mortality rates were 28.97%, 38.18%, and 55.88% in patients who had the ICU stay of seven days, 8-14 days, and 15-30 days, respectively. The mortality rate was higher in patients with prolonged length of stay. We found a statistically significant correlation between length of stay and outcome with a p-value of 0.0013 Table .In our study, the proportion of elderly patients admitted to ICU was 22.81% of total admissions. In our study, the mean age of the elderly patients admitted to ICU was 69.8 ±7.65 years which correlated with the studies conducted by Thangam et al. (70.01± 8 years) and Lankoandé et al. (71.7± 6 years) . In the In our study, 60.71% of patients were male when compared to 70.5% in a study by Lankoandé et al. In the present study, The mortality rates in elderly male and female patients were 36.97% and 35.07%. In a study by Thangam et al., mortality rates in elderly males and females were 26.08% and 23.75%. In both studies, mortality among male patients was slightly higher than females, which was statistically insignificant .In our study, neurological disorders 42.8%), renal disorders (13.26%), respiratory diseases (9.70%), infections (9.18%), and metabolic disorders (8.16%) were common causes for admissions to medical ICU. In another study done by Lankoandé et al., neurological disorders (37.9%), sepsis (10.9%), renal disorders (6.7%), and metabolic disorders (8.4%) were common causes of admission in ICU. The disease pattern of our study is similar to the study conducted by Lankoandé et al. [%, renal In our study, CVAs account for 27.50% of admissions, which is similar to 27.4% in a study conducted by Lankoandé et al. . In our In our study, we observed an increase in mortality with an increase in the number of comorbidities, which was statistically insignificant p=0.1275). Similar findings were present in a study by Thangam et al. [5. SimilaIn our study, the mean length of stay in ICU was 9.14±6.73 days, which was slightly higher when compared to 8.3±6.3 days in a study by Thangam et al. . The varIn our study, the length of ICU stay was prolonged in patients with more number of comorbidities, which was statistically significant (p<0.0001). Similar observations were present in a study conducted by Toptas et al. .The elderly are a heterogeneous population with multiple comorbidities and atypical disease presentations, which usually take a long time to diagnose. Their response to treatment is slow. Therefore, managing geriatric patients needs a multidisciplinary team and an exclusive geriatric care model .The proportion of elderly patient admissions and their mortality rate in the Medical ICU were high. Hence there is a need to have exclusive geriatric intensive care units for better care.LimitationsOur study has certain limitations. The present study included patients with medical disorders only. Patients with other conditions, such as surgical emergencies trauma-related illnesses, and critical cardiac cases were not included in this study. In this study, the post-discharge follow-up was not done.The insight over the proportion of elderly patients admitted to the ICU and their mortality rate will enable policy-makers to think of Geriatric Intensive care units. Neurological disorders (particularly CVAs) were common causes for admissions and deaths in ICU. Improvising the standards of patient care can prevent deaths due to complications of CVA, such as aspiration pneumonia. Mortality was high in patients with more comorbidities. Risk categorisation can be done based on the number of comorbidities for optimal care. There was an increase in mortality with prolonged length of stay in ICU. Length of stay can be decreased in clinically improving patients to minimise ICU-related complications. Elderly patients have multiple comorbidities and diseases with atypical presentations. Hence there is a need to redefine healthcare delivery to elderly patients in terms of triage and level of care in ICU.


HER2 aberrations in salivary gland carcinomas (SGC) as well as benefit of HER2 directed therapy have been reported in small studies. However, reliable estimates of the prevalence of HER2 positivity in SGC and its various histological subtypes are lacking.To assess the prevalence of HER2 positivity in histological subtypes of salivary gland carcinomas (SGC).in situ hybridization (ISH) and immunohistochemistry (IHC) were extracted to derive pooled prevalence estimates calculated by a random effects model. Characteristics of the studies were extracted for subgroup analysis.Studies were identified by a systematic review of the literature. Data on Fifty studies including 3372 patients were identified, providing data on sixteen histological subtypes. Based on the meta-analysis, the estimated prevalence of HER2 positivity were 43% (95% CI: 36% – 51%) in salivary duct carcinoma (SDC), 39% (95% CI: 32% – 45%) in carcinoma ex pleomorphic adenoma (CEP), 17% (95% CI: 7.5% – 33%) in squamous cell carcinoma (SCC), 13% (95% CI: 7.6% – 21%) in adenocarcinoma NOS (ADC), 6.7% (95% CI: 0.17%-32%) in poorly differentiated carcinoma, 5.5% (95% CI: 2.9% – 9.6%) in mucoepidermoid carcinoma, 4.3% (95% CI: 1.4% – 13%) in myoepithelial carcinoma, 1.8% (95% CI: 0.04%-9.6%) in epithelial-myoepithelial carcinoma, 0.45% (95% CI: 0.0097% – 18%) in acinic cell carcinoma and 0.15% (0.037% – 5.4%) in adenoid cystic carcinoma. Estimates for five additional subtypes were assessed.Prevalence of HER 2 positivity in SGC varies greatly based on histological subtype, with SDC, CEP, SCC, and ADC displaying the highest rates. Salivary gland carcinomas (SGC) are relatively rare tumors with an annual worldwide incidence of 0.07% corresponding to 52,799 cases each year according to the Global Cancer Observatory . The mosERBB2 located on chromosome 17. HER2 is overexpressed in various subtypes of SGC, but clinical trials on HER2 targeted therapy with trastuzumab or lapatanib without chemotherapy in SGC have failed to show significant clinical benefit, maybe because only a subset of the lapatinib treated patients harbored tumors with HER2 overexpression  class coded by an oncogene pression . Howeverpression . Recentlpression , 11.in situ hybridization . Various scoring systems exist for other cancer types, such as breast carcinoma and gastric esophageal adenocarcinoma (HER2 protein overexpression is measured semi-quantitatively by immunohistochemistry (IHC) and gene amplification is measured by fluorescence/silver/dual arcinoma , 13. Altarcinoma . This isarcinoma .HER2 overexpression or gene amplification seems to be a prerequisite for response to trastuzumab. Currently there is no systematic review or meta-analysis investigating the prevalence of HER2 in SGC. The aims of this review and meta-analysis are to evaluate the literature and provide prevalence estimates for HER2 in various histological subtypes of SGC.PRISMA Reporting guidelines were used.either IHC reporting semi-quantitative scores of 0, 1+, 2+, 3+ or quantitative ratios of HER2 gene copy number relative to chromosome 17 by ISH or by both IHC and ISH. Studies reporting HER2 status dichotomously (HER2 positive/negative) using the above mentioned semi-quantitative or quantitative data were eligible.Inclusion Criteria: Only studies examining human SGC tissue were included. Studies allowed were clinical trials, prospective and retrospective observational studies provided the study population was not a preselected HER2 positive cohort. HER2 status had to be evaluated by Exclusion criteria: Studies not listing which quantitative scoring methods of IHC 0 to 3+ or ISH were used to define HER2 positivity were not included. Studies not discriminating between histological subtype and HER2 status were not included. If the same dataset of patients was reported by the same author in two different publications only the newest was included. Studies reported in languages other than English, unpublished studies, case studies, conference abstracts, cell line and animal studies were all considered ineligible.Rationale for criteria: The above-mentioned inclusion criteria were chosen to gather sufficient data to evaluate HER2 positivity in specific histological subtypes, and to assess whether criteria of HER2 positivity affect the prevalence estimates.th, 2020 using the search string ) AND (HER2 or c-ERB2). The search syntaxes were adapted to those used by each respective search engine. All time periods were included. Exact search-syntax used for each search engine can be seen in PubMed, Embase, Web of Science were searched up to September 19Titles were identified by the above-mentioned search strategy, screened and assessed for inclusion in the final meta-analysis independently by KE and CDH. Discrepancies were solved by consensus. A full list of texts screened but not included as well as the reason for exclusion is listed in The eligibility criteria were designed to minimize risk of bias – especially selection bias, across studies.As the studies included are observational and not randomized controlled trials or interventional in nature, risks of bias were assessed using recommendations from COSMOS-E  .Information bias was assessed by registering methods potentially affecting how frequently the outcome were registered: Prospectively collected or archival samples, HER2 positivity criteria, IHC assay and ISH probe type. The latter were also treated as confounders together with Geographic Region.A data extraction form was used to extract equivalent information from each paper. First author, published year, geographical region, prospectively collected or archival samples, HER2 positivity criteria, IHC assay, ISH probe type and ISH type: FISH, DISH, SISH. In addition, number of patients with each histological subtype and number of HER2 positive patients as well as data on, IHC0, IHC1+, IHC2+, IHC3+, and HER2 amplification were collected.The following endpoints were predefined:The primary endpoint was HER2 positivity for each SGC histological subtype. Specific IHC data  and gene amplification status was extracted when possible. During the data collection it became clear that this specific data was only available for SDC.2 with the inverse variance method. Generalized linear mixed models were used for pooled prevalence estimates, forest plots were created and sorted based on number of patients included. Whenever sufficient data were available, subgrouping based on HER2 definition was plotted, and subgroup analysis based on probe, assay, geographical region was also conducted.Studies were included in each respective meta-analysis depending on the available data. Meta-analyses were conducted using a random effects model. The Wilson score interval method was used to calculate confidence intervals. Maximum likelihood estimator was used to estimate between study variance tauA threshold of n>60 patients was chosen for each tissue type to conduct meta-analysis, as we believe a lower number of patients would not yield a meaningful meta-analysis.The Clopper-Pearson interval was used to calculate 95% confidence intervals in tissue types not eligible for inclusion in meta-analysis.R version 4.0.0 and package meta was used.Various criteria were employed by studies to characterize tumor tissue as “HER2 positive”, and each study was labelled according to criteria employed. When data on both IHC and FISH status were reported, IHC2+ confirmed by gene amplification or IHC3+ was preferentially defined as HER2 positive.de novo and carcinoma ex pleomorphic adenoma were sufficient to conduct analysis for specific IHC status sand gene amplification. Two studies , IHC1+ 10% (95% CI: 6.4% – 15%), IHC2+ 14% (95% CI: 8.9%-20%), and IHC3+ 37% (95% CI: 28%-47%) as presented in 2 66%) heterogeneity between studies. There was no significant difference in the estimated prevalence between studies applying various probes (p=0.12).Eighteen studies were included in the analysis. HER2 amplification rate in SDC was found to be 39% (95% CI: 31-49) as shown in 2 = 80%. There was significant difference between assays p=0.0017, although the differences seemed to level off for the most commonly used assays: Prevalence of 46% (95% CI: 32%- 62%) and 44% (95% CI: 36%- 53%) were estimated for 19 and 11 studies using DAKO and Ventana assays, respectively. Prevalence of less commonly used assays are shown in Thirty-seven studies with a total of 1,105 patients were included in the random effects model. The model predicted a prevalence of HER2 positivity in SDC patients to be 43% (95% CI: 36% – 51%) depicted in There were no differences in the prevalence between studies using varying criteria for HER2 positivity (p=0.61) or conducted in different geographical regions (p=0.16).Fourteen studies were included in the random effects model with a total of 218 patients. The model predicted a prevalence of HER2 positivity in CEP patients to be 39% (95% CI: 32% – 45%) depicted in Fifteen studies were included in the random effects model with a total of 275 patients. The model predicted a prevalence of HER2 positivity in ADC NOS tumors of 13% (95% CI: 7.6% – 21%) as shown in 2 = 51% and statistically significant p=0.050. There were significant differences in the prevalence between subgroups based on criteria for HER2 positivity (p=0.0014) and geographical region (p=0.0002). The broadest criteria defining HER2 positivity as IHC2+ and IHC3+ reached prevalence estimates of 12% (95% CI: 6.4% -21%). Two American studies resulted in prevalence estimates by the random effect model of 19% (95% CI: 0.16% – 97%), four Asian studies in prevalence estimates of 4.1 (95% CI: 0.41%-30%) and nine studies from Europe in prevalence estimates of 3.3% (95% CI: 1.8% - 5.9). There was no significant difference between assays used (p=0.56).Fifteen studies with a total of 591 patients were included in the random effects model. The model predicted a prevalence of HER2 positivity in mucoepidermoid carcinoma patients to be 5.5% (95% CI: 2.9% – 9.6%) as seen in Nine studies were included in the random effects model with a total of 70 patients. The model predicted a prevalence of HER2 positivity in myoepithelial carcinoma patients to be 4.3% (95% CI: 1.4% – 13%) depicted in Ten studies with 274 patients were included in the random effects model. The model predicted a prevalence of HER2 positivity in acinic cell carcinoma patients to be 0.45% (95% CI: 0.0097% – 18%) depicted in Fifteen studies were included in the random effects model with a total of 614 patients. The model predicted the prevalence of HER2 positivity in adenoid cystic carcinoma patients to be 0.15% (95% CI: 0.037% – 5.4%) depicted in epithelial-myoepithelial carcinoma, 56 patients were included in two studies reporting a single HER2 positive tumor corresponding to a prevalence of 1.8% (95% CI: 0.04%-9.6%).The low number of patients precluded the conduction of meaningful meta-analysis for the following histological subtypes . For poorly differentiated carcinoma, 15 patients were included in four studies with one HER2 positive tumor corresponding to 6.7% (95% CI: 0.17%-32%).Seven out of 39 patients with intraductal carcinoma with one HER2 positive case corresponding to 11% (95% CI: 0.28% – 48%).One study reported on nine patients with with polymorphous adenocarcinoma, five studies included 33 patients with basal cell carcinoma, and three studies included 14 patients with oncocytic carcinoma. In all three tumor types, no HER2 positive cases were identified. Two studies reported a total of five patients with lymphoepithelial carcinoma of which zero were HER2 positive.Three studies included 50 patients clear cell carcinoma which was not HER2 positive.One study reported one patient with The present work is the first comprehensive meta-analysis providing reliable estimates of the prevalence of HER2 positivity in salivary gland carcinomas including its histological subtypes. The results are summarized in There was sufficient data in four histological subtypes, SDC, CEP, ADC NOS and mucoepidermoid carcinoma to conduct subgroup analyses of the IHC assay used and its correlation with HER2 prevalence. In three of the subgroup analyses: CEP, ADC NOS and mucoepidermoid carcinoma there was no significant difference between the IHC assays used. However, in SDC there was a significant difference based on the IHC assay used, but no difference between probes used in ISH analysis of HER2 amplification 3. The dThe criteria used to define HER2 positivity varied among studies with seven different definitions being employed. Subgroup differences between criteria applied to define HER2 positivity were also analyzed 5. A sigIn recent years, it has become common to use IHC2+ confirmed by ISH or IHC3+ as the definition of HER2 positivity as a threshold for using HER2 targeted therapies. In SGC HER2 is often evaluated by use of a HER2 scoring system developed in breast cancer with the use of a threshold chosen based upon clinical response in patients with breast cancer .Another quite unique application of HER2 testing in SGC is its use in the diagnosis of SDC, since this subtype has a higher prevalence of HER2 overexpression and gene amplification than other subtypes.There is no generally accepted standard treatment of metastatic SGC, and the role of HER2 targeted therapy in this setting is still unclear. Currently there is not sufficient data on newer HER2 targeted drugs in SGC to further define which patient population benefits from the treatment. As such, defining the specific cut-off value to decide which patients should be regarded as “HER2 positive” to receive HER2 targeted therapy remains to be answered. One step in this direction may be the HER2 scoring criteria for SGC proposed by Chatzopoulos et al. .While HER2 treatment results in survival benefits in breast, gastric and esophageal ADC, only limited data are available in SGC. Single agent HER2 directed therapy antitumor effect in patients with HER2 positive SGC is at best modest , 8. SeveBut an exact reason to why response with these drugs seem lower in SGC compared to breast cancer and gastric and esophageal ADC has yet to be found. However, HER2 still remains an important potential target for therapies. Thus, promising strategies have emerged applying dual HER2 blockage with trastuzumab and pertuzumab or combining with chemotherapy (trastuzuamb/docetaxel) or as a drug-antibody-conjugate (ado-trastuzumab-emtasine) –11.In summary, the expression of HER2 in SGC is very heterogeneous between and within histological subtypes. The prevalence of HER2 positivity ranged from 0% to 43% in 3,372 patients with sixteen subtypes of SGC. HER2 positivity was most prevalent in SDC and in some tumor subtypes derived from exocrine cells virtually no HER2 expression was reported. Prospective clinical trials are needed to further evaluate novel HER2 directed therapy and to establish the optimal definition of HER2 positivity based on treatment response in SGC with high prevalence of HER2 positivity.The original contributions presented in the study are included in the article/KE and MM-S conceived the project idea. KE and CH reviewed the literature and included studies. KE undertook data analysis. All authors assisted in writing the manuscript and interpreting results. NW, CK, and MM-S provided advice and guidance. All authors contributed to the article and approved the submitted version.CK has served in advisory boards for MSD, Bristol-Myers Squibb, and Merck Serono. MM-S has served in advisory boards for Roche, Genmab, Bayer, and Karyopharm Therapeutics and received research grants from Karyopharm Therapeutic, Puma Biotechnologies and MSD.The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Postexercise hypotension (PEH) is the immediate reduction in blood pressure (BP) of 5–8 mmHg that occurs after a single bout of aerobic exercise among adults with hypertension. Across PEH studies, there are variations in the level of rigor of the study designs and methods that limit the conclusions that can be made about PEH.To develop and then apply a methodological study quality evaluation checklist to aerobic exercise PEH studies to provide methodological guidance.n = 10 items), study (n = 23 items), and intervention characteristics (n = 5 items). We then systematically searched six databases to January 2019 to identify and then evaluate studies that: (1) enrolled adults ≥18 years with hypertension and without other chronic diseases or conditions; (2) included a bout of aerobic exercise and a non-exercise control session; and (3) were published in English.We developed a PEH checklist (PEH√list) based upon contemporary methodological study quality standards. The PEH√list contains 38 items divided into three categories: sample  were middle-aged (38.6 ± 15.6 year), overweight (26.1 ± 2.5 kg/m2) mostly men (64.4%) with elevated BP (systolic BP 129.5 ± 15.2/diastolic BP 81.0 ± 10.1 mmHg). Overall, the qualifying studies satisfactorily reported 53.9 ± 13.3% (24.2–82.8%) of the relevant items on the PEH√list. Of note, only 20.3% of the studies disclosed BP was measured following professional guidelines, 18.8% reported BP was taken by the same assessor pre- and post-intervention, and 35.5% stated participants abstained from caffeine, alcohol, and physical activity prior to testing. Half (51.5%) indicated they statistically controlled for pre-exercise/baseline BP. Meanwhile, 100% of the studies reported the setting in which the BP measurements were taken, time from the end of the exercise to the start of the BP measurements, and if relevant, the length of the ambulatory BP monitoring period.Of 17,149 potential studies, 64 qualified. Participants (Overall, the PEH√list items were not well satisfied; especially items with potential confounding effects on PEH. We contend the PEH√list provides guidance to investigators on the important methodological study considerations in PEH aerobic exercise studies that should be attended to in the future.https://www.crd.york.ac.uk/PROSPERO/], identifier [#CRD42020221996].[ Cardiovascular disease (CVD) is the leading cause of death in the United States and the world, accounting for approximately one in three deaths annually . HypertePostexercise hypotension (PEH) is the immediate reduction in BP of 5–8 mmHg that occurs after a single bout of aerobic exercise and persists for up to 24 h. PEH is clinically important because: (1) PEH occurs immediately  PEHediately ; (3) an ediately ; and (4)ediately . Also, tediately .Within the PEH literature, there is a wide range of variations in the study designs. Some of the variations include: (1) PEH studies may or may not include a control comparison ; (2) PEHEvaluation Tool for Studies Examining Postexercise Hypotension or the PEH√list. We then performed a high-quality systematic review to evaluate studies examining the BP response to acute aerobic exercise. Based on our findings, our intent was also to provide methodological guidance to investigators studying PEH.To the best of our knowledge, there is no existing easy-to-use checklist or scale that researchers can follow when designing, implementing, or reporting PEH studies. Therefore, we have developed a 38-item evaluation instrument named, the Evaluation Tool for Studies Examining Postexercise Hypotension (the PEH√list), consisting of three categories: sample, study, and intervention characteristics. See We developed an evaluation instrument named, The PEH√list consists of three sections with a total of 38 items: (1) sample characteristics (10 items); (2) study characteristics (23 items); and (3) intervention characteristics (5 items). The total number of relevant items evaluated in the PEH√list for a study was dependent on the method used for measuring BP . Accordingly, a total of 38 PEH√list items pertained to a study if both resting BP and ambulatory BP measurements were reported, 29 PEH√list items pertained to a study if only resting BP was reported, and 33 PEH√list items pertained to a study if only ambulatory BP was reported. In addition, we have selected 13 core items that are shaded in gray in This systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines . The proData were extracted using a standardized coding form and coder manual we adapted for PEH studies . Coders Descriptive statistics were calculated for the baseline characteristics of the sample in the qualifying studies. For each of the PEH√list items, the reporting rate was calculated as (the number of studies satisfactorily reporting this item/the number of studies to which this item was deemed relevant) × 100%. For each of the studies included, the PEH√list study score was calculated as (the number of items reported/by the number of relevant items) × 100%. We also compared the PEH√list study scores against a validated study quality scale score, the Downs and Black Checklist , by perfThe initial search resulted in 27,921 potentially qualifying studies. An additional 34 records were identified through manual searches. After triaging, 64 studies qualified. See n = 1,511) consisted of young to middle-aged (38.6 ± 15.7 years) healthy adults who on average, were overweight (body mass index 26.1 ± 2.5 kg/m2) and had no chronic conditions other than hypertension (129.5 ± 15.2/81.0 ± 10.1 mmHg). Over half of the participants were men , and nearly half were physically inactive . In addition, only 12.5% of the studies (k = 8) reported the ethnicity/race of the participants. A majority  of the studies controlled for the potential influence of medications that could impact the BP response to exercise. Of these studies, less than half excluded participants if they were taking various medications. Among the studies excluded participants due to medication use, more than half  excluded participants if they were taking antihypertensive medications; a few  excluded participants if they were taking antihypertensive medication or oral contraceptive (k = 1) and lipid medication (k = 3); one study (0.04%) excluded participants who were taking any medication; and the rest  excluded participants who were taking medications that can alter lipid profile (k = 4), metabolism (k = 2), heart rate (k = 2), and the renin–angiotensin system (k = 1). For the remainder of the 53 studies, participants: (1) remained on the same medication throughout the study ; (2) were not taking any medication ; or (3) stopped taking medication by going through a washout period of 1–6 weeks before the study started . Of note, only 45.3% (k = 29) of the studies identified their participants had hypertension, however, only 30.6% (k = 11) of the studies reported following professional guidelines to classify the subjects as having hypertension.The reporting rate for each of the items in the PEH√list Part 1 is listed in k = 61) published between 1987 and 2018 (2006 ± 8) and conducted in North America , South America , Europe , Asia , and Australia . Studies included 6–109 participants (24 ± 20), and more than half contained multiple exercise arms , while 15.6% (k = 10) contained multiple control arms. Of note, only 25% (k = 16) of the studies reported they performed a sample size estimation based on BP as the primary outcome, and only six studies (9.8%) reported the procedure used for randomization.The reporting rate for each of the items in the PEH√list Part 2 is listed in k = 33) of the studies reported controlling for baseline/pre-exercise BP by including baseline/pre-exercise BP as a covariate in the statistical models comparing: (1) average BP post-exercise versus average BP post-control ; or (2) the change of BP due to exercise  versus the change of BP due to control  .When calculating PEH more than half  measured resting BP, 42.2% measured ambulatory BP (k = 27), or 6.3% measured both (k = 4). Among the 41 studies measuring resting BP, most were measured in the seated position  in the laboratory  starting 12.6 ± 11 min after the end of the exercise session and continued for 142.1 ± 247.3 min thereafter. Of the 27 studies assessing ambulatory BP, most occurred under free-living conditions  starting 27.1 ± 17.8 min after the end of the exercise sessions and continued for 20.1 ± 6.1 h. Of note, most studies  reported the model of the BP device used to measure BP. However, studies rarely disclosed they followed protocols recommended by professional guidelines when measuring resting BP  or ambulatory BP . The studies assessing ambulatory BP rarely  disclosed whether a familiarization session was performed prior to the start of experiments, or a calibration check was performed . In addition, only 31.3% (k = 20) of the 64 studies assessing resting and/or ambulatory BP asked participants to abstain from physical activity, alcohol, and caffeine prior to experiments.Regarding the measurement of BP, 64.1% of the studies (k = 34) reported the time of day of the exercise and control sessions, with most of the sessions occurring in the morning between 7:00 am and 12:00 pm . There were 99 exercise arms in the included studies. The majority of exercises were performed in a laboratory setting , two studies (4.0%) performed exercises in aquatic setting, and others were in workplace , thermal bath , and a combination of laboratory and outdoors . There were 25 studies (39.1%) that reported the temperature that the participants exercised in with the lowest temperature range being 15–22°C in k = 82) and vigorous  intensity measured by various methods such as peak oxygen uptake, maximal oxygen uptake, and heart rate maximum (see k = 61) or treadmill . Among the 61 control arms, control sessions on average lasted 48.3 ± 58.6 min with seated rest being the most common   of the studies were of low risk, 75% (k = 48) had some concerns, and 7.8% (k = 5) were of high risk. In the Domain of Bias Arising from the Deviations from Intended Interventions, 64.1% (k = 41) of the studies were of low risk, 21.9% (k = 14) had some scored some concern, and 14.1% (k = 9) were of high risk. In the Domain of Bias Due to Missing Outcome Data, 93.8% (k = 60) were of low risk, 6.2% of the studies (k = 4) had some concerns, and no studies were of high risk. In the Domain of Bias in Measurement of The Outcome, 85.5% of the studies (k = 55) were of low risk, 14.5% (k = 9) had some concerns, and no studies were of high risk. In the Domain of Bias in Selection of The Reported Result, 96.8% of the studies (k = 62) were of low risk, 3.2% (k = 2) of the studies had some concerns, and no studies were high risk. Please see For the determination of the overall risk of bias using the Revised Cochrane Risk-of-Bias Tool for Randomized Trial , eight sk = 20) exhibited low methodological quality, most of the studies  exhibited moderate methodological quality (k = 44), and no study scored high methodological quality. Meanwhile the average PEH√list study score was 53.9 ± 13.3%. Among the 64 studies, two reached a high checklist study score (81.0 ± 0.02%), 36 reached a moderate checklist study score (62.1 ± 0.08%), and 26 had low study scores (41.2 ± 0.06%). Please see p = 0.009). Please see On the Downs and Black checklist, studies scored averaged 55.6 ± 10 (37.9–79.3%). Of these, 31.3% , 36 reached a moderate checklist study score (62.1 ± 0.08%), and 26 reached a low checklist study scored (41.2 ± 0.06%). Of the three sections of PEH√list, Part 3-Intervention Characteristics  had the n = 13) that were reported ∼<50% of the time relevant to a given study were: (1) 20% followed standard protocols for measuring BP, such as the American College of Cardiology and American Heart Association guidelines, to ensure the accuracy of BP measurements  22%urements ; (3) 25%urements ; (4) 31%urements ; and (5)urements . Clearlyp = 0.009), indicating the PEH√list can be used as a methodological study quality evaluation tool specifically designed for PEH studies.There are some limitations to the current study. First, our review only involved aerobic exercise PEH studies . HoweverDespite these limitations, our study has several strengths. To the best of our knowledge, our study is the first to systematically review the aerobic exercise PEH study methodology. We systematically searched six different databases following PRISMA guidelines. The development of the PEH√list is based on our  and otheIn conclusion, founded upon a high-quality, contemporary systematic review, we have stringently evaluated aerobic exercise PEH studies with the PEH√list and identified fundamental study design considerations that need improvement. Future researchers should consider using our PEH√list, or at minimum the core items, in conjunction with methodological study quality standards when designing and implementing PEH studies as well as reporting their results.The original contributions presented in the study are included in the article/CD participated in the design of the study, data extraction, and interpretation of details, performed the statistical analysis, and drafted and revised the manuscript critically for important intellectual content. YW participated in the design of the study, data extraction, and interpretation of details and revised the manuscript critically for important intellectual content. LP participated in the design of the study and revised the manuscript critically for important intellectual content and final approval of the version to be published. All authors contributed to the article and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Respiratory diseases are leading cause of morbidity and mortality worldwide imposing significant global health burden. The admission rate of patients is the indication of the overall workload in the ward. The aim of this study was to find the prevalence of admission of patients in the pulmonology ward among patients visiting pulmonology department of a tertiary care hospital.A descriptive cross-sectional study was conducted at Tribhuvan University Teaching Hospital. Medical records of all patients visiting pulmonology department and admitted in pulmonology ward from May 2018 to April 2020 were retrospectively reviewed. Data entry and analysis was done in SPSS version 20.0. Descriptive statistics were performed.A total of 30,480 patients visited the pulmonology department in the two-year study period. Out of them, 1296 (4.25%) patients were admitted in the pulmonology ward. Eleven respiratory diseases were identified as primary causes for admission. Acute exacerbation of chronic obstructive pulmonary disease (44.5%), pneumonia (26.3%), tuberculosis (11%), lung cancer (5%) and bronchiectasis (3.9%) ranked top five causes for admission.Respiratory diseases impose tremendous burden in health care setting. Acute exacerbation of chronic obstructive pulmonary disease, pneumonia and tuberculosis remain an important cause of respiratory admissions in our study. Respiratory diseases constitute an important global health burden. Acute respiratory infections, pneumonia, tuberculosis, obstructive and restrictive lung diseases, pleural diseases, and malignancies are common respiratory conditions for hospital admission.1 The forum of international respiratory societies (FIRS) estimated that 65 million people have moderate to severe COPD resulting in 3 million deaths per year, making it third leading cause of death worldwide.2 Currently, asthma affects an estimated 334 million people worldwide and is projected to increase to 400 million by the year 2025.3 In 2015, 10.4 million people developed TB with 1.4 million global deaths were reported.4Chronic obstructive pulmonary disease (COPD), lower respiratory tract infections, lung cancer and tuberculosis have been identified as top four respiratory diseases among ten leading causes of death worldwide.The aim of this study was to find the prevalence of admission of patients in the pulmonology ward among patients visiting pulmonology department of a tertiary care hospital.This is a descriptive cross-sectional study conducted in the department of Pulmonology at Tribhuvan University Teaching Hospital (TUTH), a tertiary referral center in Kathmandu, Nepal. Ethical approval was obtained from Institutional Review Committee, TUTH (Reference no. 158/ (6-11) E2/076/077). All patients admitted in pulmonology ward from May 2018 to April 2020 were included in the study. Medical records of all patients admitted in pulmonology ward of TUTH over the period of two years were retrospectively reviewed and information on demographic data, pattern of respiratory diseases among admitted patients, co-morbidities, duration of hospital stay, and treatment outcome were retrieved. Treatment outcome was further categorized into discharge, intensive care unit (ICU) admission, leave against medical advice (LAMA) and mortality.Data were extracted from in-hospital patient records. Data entry and analysis was done in Statistical Package for the Social Sciences (SPSS) version 20.0. Descriptive analysis was done.A total of 30,480 patients visited the pulmonology department in the two-year study period. Out of them, 1296 (4.25%) patients were admitted in the pulmonology ward. Eleven respiratory diseases were identified as primary causes for admission in respiratory ward. Acute exacerbation of chronic obstructive pulmonary disease (COPD) was the most common condition for admission followed by pneumonia and tuberculosis (TB) respectively .The mean age of the patients was 60.36±18.44 years with range from 16 to 103 years. Among the patients admitted, the highest number of patients was in age group 60-74 years in both sexes. The sex distribution of patients was similar in both sex with 659 (50.8%) male and 637 (49.2%) females .Nearly 55% of patients had one of the 13 co-morbidities. Acute kidney injury (AKI) was the most common co-morbidity seen in 100 (7.7%) patients. Other common co-morbidities were cardiac disease in 95 (7.3%), diabetes mellitus in 93 (7.2%), hypertension in 78 (6%), anemia in 61 (4.7%) and post TB sequelae in 40 (3.1%) patients .*OSAHS- Obstructive sleep apnea hypopnea syndrome, ϯCLD- Chronic liver disease, Ŧ HIV- Human immune deficiency virus, || CKD- Chronic kidney disease, ¶AKI- Acute kidney injuryThe mean duration of hospital stay was found to be 8.8±6.18 days with range from 3 to 33 days. The highest duration of hospital stay was seen in patients with pneumothorax which was 11.12±7.51 days while lowest for acute severe asthma with duration of 5.62±2.50 days.More than 90% of patients (n=1196) admitted in respiratory ward got discharged. Fifteen (1.2%) patients left against medical advice (LAMA), 60 (4.6%) patients deteriorated and required subsequent admission in intensive care unit (ICU) while 25 (1.9%) patients had in-hospital mortality. Out of total ICU admissions, the highest admission rate was 58.3% (n=35) seen in patients with acute COPD exacerbation. The highest mortality rate was also seen in COPD patients which accounted to 36% (n=9) of total in-hospital mortality .5 in a teaching hospital of Nepal, respiratory diseases (31.73%) were the most common cause among 1040 admissions in medical ward. The mean age of patients in respiratory ward was 60.36±18.44 years with range from 16 to 103 years. In a similar study done at a tertiary centre in India over a period of two years by Kumar A et al,6 the mean age for admission was found to be 48.6±12 years. Sachdeva R et al7 in a study done at a university hospital in India observed 50.64±15.71 years. We found a similar proportion of male and female patients in our study. There were 50.8% male and 49.2% female patients. In contrast to our study, Kumar A et al6 observed a male preponderance for admission with 70% males and 30% females out of 3337 patients who got admitted to pulmonary medicine ward. Higher proportion of male patients were also observed by Sachdeva R et al7 and also in a study done in Nigeria by Umoh VA et al8 which observed male to female ratio for admission to be 3.5:1 and 1.7:1 respectively. This discrepancy in sex distribution among the patients could be implicated to the genetic differences and health seeking behavior and practices among male and female towards lung disease. We found that 11 respiratory diseases were primary causes for admission in respiratory ward. COPD, pneumonia, tuberculosis, lung cancer and bronchiectasis were the top five causes of admission in respiratory ward while combined prevalence of other diseases like pneumothorax, interstitial lung disease, lung abscess, empyema, asthma and hydatid cyst comprised of less than 10% of total admissions.We found that 1296 patients with respiratory diseases were admitted in respiratory ward over two years. In a study done by Pokharel BR et al6 which found COPD (29.3%), TB (14.8%), pneumonia (9.3%), asthma (5.5%) and bronchiectasis (2.8%) as top five causes for admission in respiratory ward. Sachdeva R et al7 also reported tuberculosis, COPD, pneumonia, lung cancer and asthma as major causes for admission. Similar findings were reported in a study done by Alamoudi OS et al9 in Saudi Arabia and Umoh VA8 in Nigeria. Though the top five primary diseases for admission in respiratory ward in our and other studies were similar, there was striking variation in prevalence of these diseases among these studies. Another distinct contrasting feature in our study as compared to others is the lower prevalence of asthma as seen in 0.8% patients. The differences in occurrence of diseases could be implicated to diverse geographic and environmental variations among these regions.Acute exacerbation of COPD was the most common respiratory condition seen in 44.5% patients followed by pneumonia in 26.3%, tuberculosis in 11%, lung cancer in 5% and bronchiectasis in 3.9% of patients. These findings are consistent with study done by Kumar A et al10 Tobacco smoking, indoor and outdoor air pollution are major contributing factors for higher prevalence of COPD in Nepal. Biomass fuel is used widely used across Nepal for cooking purposes in more than 87% of households in rural areas as compared to 52% in urban areas.11 In 2016, the Global burden of disease study estimated the prevalence of COPD in Nepal as 4,810 per 1,00,000 which was accountable for 5.72% of all deaths.13The higher prevalence of COPD in our study could be related to the upsurge in national prevalence of COPD in recent years. In a study on prevalence of selected non-communicable diseases in Nepal conducted by the Nepal Health Research Council (NHRC), COPD had the highest prevalence (11.7%) among non-communicable diseases reported in the participants.6 found hypertension and diabetes mellitus as the commonest co-morbidities which ranked third and fourth in our study. Umoh VA et al8 in Nigeria observed HIV/AIDS and hypertension as the commonest co-morbidities.A myriad of co-morbidities were found to be associated with respiratory diseases. More than 55% of patients had one of the 13 co-morbidities among which acute kidney injury was the most common co-morbidity seen in 7.7% patients followed by cardiac disease in 7.3%. On contrary, Kumar A et al14 in Nepal reported more than half of the patients presenting to hospital with COPD had features of chronic cor pulmonale as shown in echocardiography.Pre-existing cardiac diseases was the second most common co-morbidity seen in our study. Concomitant respiratory and cardiac diseases result in overlapping symptoms of chest pain and dyspnoea in patients. Features of chronic cor pulmonale was seen in 29.3% of 577 COPD patients. A study done by Shrestha B et al6 but they reported lower average duration of 5.2 ± 2.5 days than in our study. Sachdeva R et al7 also observed lower duration of hospital stay which was 6.91 ± 5.14 days while higher duration was observed by Umoh VA et al8 which was 15.4 ± 6.4 days but with similar range for duration (3 and 35 days) as observed in our study.The mean duration of hospital stay was 8.8 ± 6.18 days with range from 3 to 33 days. The highest duration of hospital stay was seen in patients with pneumothorax (11.12 ± 7.51 days) while lowest in acute severe asthma (5.62 ± 2.50) days. Similar range for duration of hospital stay (2 to 28 days) was observed by Kumar A et al6 and Umoh VA et al8 but higher in-hospital mortality as compared to our study were reported in both of these studies.More than 90% of patients admitted in respiratory ward got discharged, 1.2% patients left against medical advice (LAMA), 4.6% required subsequent ICU admission while 1.9% patients had in-hospital mortality. Similar proportion of discharges were reported by Kumar A et alRespiratory diseases impose an immense burden in health care setting. COPD, pneumonia, tuberculosis, lung cancer and bronchiectasis remained top five causes of respiratory admissions in our study. This is a hospital-based study from a tertiary referral center in Nepal potentially serving as preliminary findings upon which future studies can be based.


IntroductionThe objective of our study was to compare the 30-day post-operative outcomes of laparoscopic sleeve gastrectomy (LSG) and laparoscopic Roux-en-Y gastric bypass (LRYGB).Materials and Methods2 (morbidly obese), age 18 to 65 years and with failure of conservative treatment were included. Group I patients underwent bariatric surgery using LRYGB technique while group II patients underwent bariatric surgery using the LSG technique. All patients were followed 30 days after surgery to determine early post-operative outcomes.This randomized controlled study contained patients who underwent bariatric surgery from June 13, 2018 to October 12, 2019. A total of 116 patients having body mass index (BMI) > 35 kg/mResultsThe demographic profile, such as age and BMI, was similar between the groups. The mean operating time was 72 ±12 minutes in the LSG group and 156 ± 18 min in the LRYGB group . Major complications were seen in five (8.62%) patients in LSG patients and in four (6.89%) patients in LRYGB group . Minor complications were seen in 21 (36.2%) patients in LSG group and in 19 (32.75%) patients in LRYGB group . The length of stay in the hospital in LSG group was 6.2±4.2 versus 9.4± 4.6 .ConclusionBoth LRYGB and LSG are effective and safe bariatric procedures with a similar incidence of major complications. However, LSG is associated with shorter operative time and hospital stay. Long-term follow-up studies are required to compare the effectiveness of these procedures. Obesity is one of the most challenging chronic diseases in the western world as well as in Pakistan . Half ofObesity is challenging to control by medical therapy and drug treatment. The most effective way to treat obesity is bariatric surgery . The forLaparoscopic Roux-en-Y gastric bypass (LRYGB) is a “gold standard” bariatric surgical procedure. LRYGB surgery provides two surgical modifications: (i) it restricts the gastric capacity and (ii) it diverts the swallowed nutrients away from the proximal part of the small intestine . The draRecently there is much attention gained by laparoscopic sleeve gastrectomy (LSG), which was described by Regan et al. . LSG is 2 (morbidly obese), with failure of conservative treatment. The exclusion criteria were severe indicative gastroesophageal reflux disease (GERD), conversion of another bariatric procedure, large hiatal hernia, and patients with inflammatory bowel disease.This randomized controlled trial (NCT04779723) containing 116 patients who underwent bariatric surgery was conducted from June 13, 2018 to October 12, 2019. Inclusion criteria were patients of age 18 to 65 years, body mass index (BMI) kg/mApproval of the study was taken from the research evaluation unit of the hospital. All patients were informed about the risks and benefits of both operations, and a written informed consent taken from individual patients before including them in the study and by insuring them the confidentiality of their data and identity.All morbidly obese patients were distributed into two groups using the computer-generated random number table. Fifty-eight patients allotted for the LSG group and another 58 patients to the LRYGB group Figure .LRYGB technique was performed by placing four to six trocars, a 150-cm ante-colic Roux-limb gastric pouch (30 to 50 ml) was created with linear stapled or circular stapled gastro-jejunostomy based on the surgeon preference, A 50-cm long biliopancreatic limb was chosen. Passive drainage was kept near to the gastro-jejunostomy. On the fourth post-operative day, the drainage was removed. For LSG, 35 Fr bougie was used for the calibration of a gastric tube. A 3 to 6 cm of longitudinal incision of the stomach was done at pylorus to the angle of His. After completing the resection, the staple line was sewn using absorbable suture. The abovementioned standardized procedures were done in all patients.Data analysis was carried out by SPSS v23.0 , quantitative variables were compared between the LSG and LRYGB group using an independent sample t-test. For qualitative variables, frequency (%) was calculated and a comparison between the groups was made using Chi-square test. Statistical p-value < 0.05 indicated as significant.2 versus 47.3 ±4.6 kg/m2 in LSG and LRYGB, respectively . There were 22 (37.98%) hypertensive, 32 (55.1%) diabetic, and 39 (67.2%) dyslipidemia patients in LSG group versus 26 (44.28%) hypertensive, 28 (48.27%) diabetic, and 42 (72.41%) dyslipidemia patients in LRYGB group. Detailed data are presented in Table Mean age was 46.6 ±12.3 years in the LSG group and 43.4 ±11.2 years in the LRYGB group . Mean BMI was 46.2 ± 4.2 kg/mThe mean operative time was 72 ± 12 min in LSG and 156 ± 18 min in LRYGB group . The length of stay in LSG group was 6.2 ± 4.2 days versus 9.4 ± 4.6 days in LRYGB group . Major complications were diagnosed five (8.62%) patients in LSG patients and in four (6.89%) patients in LRYGB group . Leakage was diagnosed in three (5.16%) patients in LSG group and in one (1.72%) patient in LRYGB group , bleeding was diagnosed in one (1.72%) patient in LSG group versus one (1.72%) patient in LRYGB group . Wound infections were diagnosed in one (1.72%) patient in LSG group and in two (3.44%) patient in LRYGB group . There was no operative mortality. Minor complications were diagnosed in 21 (36.2%) patients in LSG group and in 19 (32.75%) patients in LRYGB group . Hair loss and nausea were commonest complications, with an insignificant difference between the groups. Detailed perioperative and post-operative data are shown in Table The LSG and LRYGB are the commonest techniques of performing bariatric surgery. These procedures are safe and effectively reduces the weight and comorbidities in long-term follow-up ,12. ReceIn the present study, we found that LSG is safer than LRYGB as it has a statistically short operating procedure time  and hospital stay . We also found an overall lower rate of complication in the LSG group but it was non-significant in both groups.Studies conducted on the short-term outcome of the LRYGB and LSG, also reported higher operative time and long hospital stay using the LRYGB technique, but with insignificant difference . Li et aOur results are almost similar to the FINISH trial, which exclusively studied the post-operative complications between LSG and LRYGB groups . The triAnother study conducted by the national surgical quality improvement program (NSQIP) reported that risk adjustment for LSG is 1.32 times lesser than LRYGB . Even thA meta-analysis study conducted on 30-day complications comparison between LSG and LRYGB by Kumar et al. concluded that LSG had lower odds of leak and death than LRYGB and is safe regarding the short-term outcomes .Limitations of the studyThe major limitation of the present study is the small sample size and we followed the patients only for 30 days. There is a need to conduct large-scale studies from high volume centres to further validate the gold standard technique for bariatric surgery.Both LRYGB and LSG are effective and safe bariatric procedures with a similar incidence of major complications. However, LSG is associated with shorter operative time and hospital stay. Long-term follow-up studies are required to compare the effectiveness of these procedures. Based on the present study results, we suggest to prefer LSG as a preferred bariatric procedure.


The aim of this study is to assess the efficacy and safety of ruxolitinib in patients with myelofibrosis.From 15 centers, 176 patients  were retrospectively evaluated.The median age at ruxolitinib initiation was 62 (28–87) and 100 (56.8%) of all were diagnosed as PMF. Constitutional symptoms were observed in 84.7%. The median initiation dose of ruxolitinib was 30 mg (10–40). Dose change was made in 69 (39.2%) patients. Forty seven (35.6%) and 20 (15.2%) of 132 patients had hematological and nonhematological adverse events, respectively. The mean spleen sizes before and after ruxolitinib treatment were 219.67 ± 46.79 mm versus 199.49 ± 40.95 mm, respectively (p < 0.001). There was no correlation between baseline features and subsequent spleen response. Overall survival at 1-year was 89.5% and the median follow up was 10 (1–55) months. We could not show any relationship between survival and reduction in spleen size (p = 0.73).We found ruxolitinib to be safe, well tolerated, and effective in real-life clinical practice in Turkey. Ruxolitinib dose titration can provide better responses in terms of not only clinical benefit but also for long term of ruxolitinib treatment. Myelofibrosis (MF) is a chronic myeloproliferative neoplasm that is characterized by extensive fibrosis of the bone marrow, splenomegaly, and constitutional symptoms such as night sweating, weight loss, and fever . MF can present as a primary (PMF) or secondary disease after essential thrombocythemia (ET) or polycythemia vera (PV) . Prognosis is assessed by the several prognostic scoring systems such as the International Prognostic Scoring System (IPSS), dynamic-IPSS (DIPSS), and DIPSS-plus [1]. Life expectancy ranges between 2–11 years according to IPSS [1]. Janus kinase 2 (JAK2) is a member of intracellular, nonreceptor tyrosine kinases (JAK family) that transduce cytokine mediated signals via the JAK-signal transducer and activator of transcription (STAT) pathway . About 65% of MF patients carry a gain of function mutation in JAK2 gene (JAK2 V617F) [1]. Mutations in the calreticulin and The myeloproliferative leukemia virus oncogene (MPL) gene, which also lead to dysregulated JAK/STAT signaling, is identified in patients who do not have the JAK2 mutation [1]. Ruxolitinib is an oral JAK1/JAK2 inhibitor that has demonstrated significant improvement in splenomegaly and constitutional symptoms, and an increase in overall survival (OS) in COMFORT-I and COMFORT-II studies in patients with MF [6–10]. Therefore, ruxolitinib was approved by FDA for the treatment of intermediate- and high-risk MF patients. The JUMP trial which was constructed as phase 3b expanded access trial, covers patients in countries without access to ruxolitinib outside of a clinical study and it also includes patients who classified as intermediate-1 risk. In this study, 62% of patients achieved a > 50% of reduction from baseline of palpable spleen length. The most common adverse events were anemia, thrombocytopenia, primarily grade 1/2 diarrhea, pyrexia, fatigue, asthenia, and infections [11].In the literature, there are some reports that evaluated the efficacy and safety of ruxolitinib outside of clinical trials in patients with MF. These studies reported reduction in spleen size and improvement of constitutional symptoms [12–14].We designed this multicenter study to retrospectively evaluate the efficacy and safety of ruxolitinib in Turkish patients with MF in the real-life clinical practice.This study was designed as a retrospective, multicenter study from Turkey, and approved by Ege University Ethical Committee with number of 16–6.1/9. Across all of Turkey, 15 centers were enrolled in the study. We reviewed the medical records of 176 patients with MF from December 2012 to November 2017. The primary objective of the study was the evaluation of the efficacy and safety of ruxolitinib in patients with myelofibrosis in Turkey.Patients’ ≥ 18 years of age who diagnosed PMF, post-PV or post-ET MF were classified as intermediate- or high risk disease stratified based on the DIPSS or DIPSS plus were included in this study . Diagnosis was confirmed according to the 2008 World Health Organization (WHO) criteria and post-PV or -ET MF was diagnosed in accordance with the criteria of the International Working Group of Myelofibrosis Research and Treatment .In Turkey, ruxolitinib was firstly obtained from the official compassionate use program approved by the Turkish health authorities since October 2011. In June 2016, the commercial use of ruxolitinib was approved and started, and compassionate use program was ended. Patients were only allowed to enter this program if they had a platelet count of 100.000/mm3 or higher. All patients provided written informed consent before the use of this drug. The initial dosage was determined by the physicians according to patient’s clinical condition and platelet count at baseline, ranging from 5 to 20 mg twice daily. The dosage was adjusted every 2–4 weeks based on the platelet counts and the severity of nonhematological toxicities if existed.A special case report form was used for data collection. Patients’ age of diagnosis, sex, constitutional symptoms, spleen size before and after ruxolitinib treatment, and other clinical parameters were noted. We also collected data of side effects, leukemic evolution, and death.Response to treatment was reported by the primary treating physicians and analyzed as categorical variables , and as a continuous variable (decrease in spleen size). Spleen length was assessed with abdominal ultrasonography or palpation on physical examination.All the statistical analyses were performed by using the data obtained from the patients’ files. Demographic and disease characteristics of the patients were summarized for all patients using descriptive statistics.Statistical analyses were performed using SPSS v.16.0 . The variables were first assessed by Kolmogorov–Smirnov testing in terms of normal distribution. The results were provided as mean ± SD for normally distributed variables and as median (min-max) for nonnormally distributed parameters. Categorical and continuous variables were compared with chi-square and Mann–Whitney U tests, respectively. Logistic regression analysis was performed to correlate spleen response and constitutional symptom response with several baseline features, such as, age > 65 years, sex, diagnostic subgroups, DIPSS score, leukocytosis (> 25.000/µL), hemoglobin < 10 g/dL, platelet < 200.000/µL, blast cells > 1%, JAK2V617F mutation status, and time between diagnosis to ruxolitinib treatment. All p-values were two-tailed and statistical significance was set at the level of p < 0.05.Overall survival (OS) was defined from the date of ruxolitinib start to the time of death or last follow-up. OS evaluation was performed using the Kaplan–Meier method.From 15 centers, 176 patients  were enrolled the study. Patient demographic information and baseline clinical characteristics were shown in Table 1. The median age at diagnosis and ruxolitinib initiation was 59 years (range: 19–83) and 62 years (range: 28–87), respectively. The median interval between diagnosis and the initiation of ruxolitinib was 41.5 months (range: 0–342). One hundred of patients (56.8%) were diagnosed with PMF, 47 (26.7%) and 29 (16.5%) of patients were post-PV MF and post-ET MF, respectively. Hepatomegaly was detected in 89/171 of the patients (52%) and constitutional symptoms were observed in 149/176 (84.7%). Pruritus and minor neurological symptoms were observed in 26.1% and 20.5% of the patients, respectively. Thrombosis  before diagnosis was detected in 13.1%, whereas bleeding was a more rare complication before diagnosis affected 6.3% of the patients. Most common sites of bleeding were epistaxis, gastrointestinal, and cerebral hemorrhage reported in 5, 2, and 2 patients, respectively. Gingival and urinary hemorrhage was observed in 2 patients. Only 2 patients (1.1%) had concomitant cancer history. These were cholangiocellular cancer in one patient and gastric cancer in the other patient. One-hundred and thirteen of all patients (64.2%) were positive for the JAK2 mutation. Eighty patients’ blood analyzed for the MPL mutation. MPL mutation was detected in 6 (7.5%) of 80 patients. Conventional cytogenetic analysis was applied in 31 patients. Twenty three patients had normal karyotypes and 8 had complex karyotypes.Antiplatelet, androgen, and steroid treatments were used in 94 (53.4%), 18 (10.2%), and 11 (6.3%) patients, respectively. Seven patients (4%) had history of erythrocyte stimulating agent treatment. Splenectomy and stem cell transplantation was rarely used, in 7 (6%) and 1 patient, respectively.Cytoreductive treatment was used in 153 (86.9%) patients. The most common drug as the first line treatment was hydroxyurea . Twelve (7.8%) of 153 received anagrelide therapy, 8 (5.2%) interferon and 2 (1.3%) thalidomide. Second line treatment was used in 41 (23.3%) patients. Anagrelide and interferon were the most common second line treatment agents . Only 8 patients (4.5%) had third line treatment. The most common agent was interferon (n = 5).The median initial dose of ruxolitinib was 30 mg per day (range:10–40 mg).The initial ruxolitinib doses were 20 mg BID, 15 mg BID, 10 mg BID and 5 mg BID in 67 (38.1%), 36 (20.5%), 46 (26.1%), and 27 (15.3%) patients, respectively. Ruxolitinib dose modifications were necessary in 46% of 150 patients. Ruxolitinib treatment details were given in Table 2. After dose modifications, the median ruxolitinib doses achieved was still 30 mg per day (range: 10–40 mg). The maximum ruxolitinib doses achieved were 20 mg BID, 15 mg BID, 10 mg BID and 5 mg BID in 52 (29.5%), 55 (31.3%), 62 (35.2%), and 7 (4%) patients, respectively.Data of improvement in constitutional symptoms and spleen response were available in 152 (86.3%) and 150 (85.2%) patients, respectively. Improvement in constitutional symptoms was seen in 136/152 (89.4%) patients. A reduction in splenomegaly was seen in 102/150 (68%) patients.The mean spleen sizes before and after ruxolitinib treatment were 219.67 ± 46.79 mm versus 199.49 ± 40.95, respectively (p < 0.001). A ≥ 50% reduction from baseline in palpable spleen length was seen in 17/39 (43.5%) patients at any time during the study. Mean percentage change from baseline to week 12 in ultrasonographic spleen length showed in Figure 1. Mean percentage change from baseline in palpable spleen length showed in Figure 2. Among baseline features that were tested for correlation with subsequent spleen response and constitutional symptom response, none were significantly associated with these. The data showed in Table 3. There was no correlation between maximum ruxolitinib doses achieved and reduction in spleen size. Adverse events data were available in 132 (75%) of all patients. Forty seven (35.6%) of 132 patients had hematological and 20 (15.2%) had nonhematological adverse events. Adverse events are illustrated in Table 4. Patients who had anemia treated with red blood cell transfusions. For management of thrombocytopenia, ruxolitinib dose reduction was performed. Nonhematological adverse events  were treated with supportive care. Infections were treated with antimicrobial therapy.Overall, 26 patients (14.8%) died because of leukemic transformation (n = 3), cardiac diseases (n = 4), pneumonia/sepsis (n = 8), acute respiratory distress syndrome (n = 1), cholangiocellular cancer (n = 1), bleeding (n = 3), and disease progression without leukemic transformation (n = 6). Death occurred after a median ruxolitinib exposure of 9.4 months (1–45.1 months); in no case the death was directly attributed to therapy. Estimated OS at 1-year was 89.5% and the median follow up was 10 (1–55) months, as shown in Figure 3. Estimated OS at 3-year from ruxolitinib start was 72.3% in patients achieving a spleen response and 68.3% in patients without a spleen response. The mean OS was 45.05 ± 2.8 months in patients who had reduction in spleen size, whereas the mean OS was 38.24 ± 4.1 months in patients who had no reduction in spleen size. Statistical significance was not observed between OS and spleen response (p = 0.73), as shown in Figure 4.The aim of this retrospective and multicenter study was to evaluate the efficacy and safety of ruxolitinib in Turkish patients with MF in the real-life clinical practice. We evaluated 176 patients from 15 centers across all of Turkey.In our study, the median age at ruxolitinib treated patients (62 years) was slightly lower than literature (61.8–74 years) . Sex and subtype of myelofibrosis were similar to literature . Intermediate-2 risk patients  were the most common prognostic group according to DIPSS in this cohort, this finding was compatible with the literature (30%–62.4%) . In COMFORT-I and II trials, patients were intermediate-II and high risk group according to IPSS . In our study, 32.1% of 137 patients who received ruxolitinib were intermediate-1 risk according to DIPSS and it was higher than literature . This higher rate may be associated with limited effective treatment options for MF in the real life practice. In the literature, rates of IPSS low and intermediate-I risk group patients in real-life studies were between 11.8% and 31% . One should not forget that most of our patients are from the compassionate use program, which means that they were allowed in special conditions.Most patients in this study experienced reduction in spleen size (68%) and improvement in constitutional symptoms (89.4%). These results were comparable with previous study reported by Ellis et al. [14]. The rate of patients achieving 50% or more reduction in palpable spleen size in this study was similar to literature . In this study, both ultrasonographic and palpable spleen size were evaluated. In the real-life setting, physical examination of a patient is performed by various physicians in outpatient clinics. Ultrasonography is a common, simple, and cheap imaging technique. Although we did not evaluate spleen volume with ultrasonography in all patients, spleen size reduction after ruxolitinib treatment was significant in both physical and ultrasonographic examination.The median initial dose of ruxolitinib was 30 mg per day in our analysis and this dose was compatible with literature  but dose modification rate was lower than reported in other studies (46% vs. 54%–88.9%) . Lower dose modification rate in our study might be associated with lower initial dose rate than other studies. In our study, 38.1% of patients started at the dose of 20 mg BID, whereas 54.2%–63.6% of patients started at the dose 20 mg BID in other studies . After dose modifications, the median dose of ruxolitinib was still 30 mg per day in this study. There was no correlation between maximum ruxolitinib doses achieved and spleen response.The most common hematological adverse events were anemia (24.2%) and thrombocytopenia (18.9%) in our study as expected. Anemia was relatively lower than other studies (39.7%–62.7%) . Thrombocytopenia was slightly lower than others (25.5%–40.5%) . The most common nonhematological adverse events were abnormal hepatic (3%) function tests and infections (5.3%) in this study. These rates were much lower compared to other studies . The lower rates of toxicities in our study might be related to lower initial dose of ruxolitinib and close monitorization of patients in terms of toxicities. Since it is retrospective study, adverse event data might have been reported less frequently.Baseline factors were not associated with spleen response and constitutional symptom response in our study. In a retrospective study, high/intermediate-2 IPSS risk, a large (≥ 10 cm below LCM) splenomegaly, transfusion dependency, platelet count < 200 ´ 109/L, and a time-interval between MF diagnosis and RUX start > 2 years were significantly associated with lower spleen response [20]. The same study was also evaluated pre-treatment factors negatively correlating with symptom response. In multivariate analysis, a baseline total symptom score (TTS) > 20 had a significantly lower probability of achieving a symptoms response at 6 months. In our study, because numbers of intermediate-1 DIPSS risk patients were higher than other studies, more patients who received ruxolitinib had less advanced disease. The lack of correlation between the spleen response and some baseline factors can be explained with higher rate of less advanced disease and relatively small patient population. The estimated OS at 1 year was similar to JUMP trial (89.5% vs. 94%) [11]. The estimated OS at 3 years from ruxolitinib start was 72.3% in patients achieving a spleen response and 68.3% in patients without a spleen response. Although these rates were comparable with literature , statistical significance was not shown in our study (p = 0.736) [20]. Lower initial dose of ruxolitinib in our study might be associated with slightly lower spleen response. There are some limitations of this study. Firstly, this is a retrospective study so, some of the data was not found because of inadequate records. Secondly, a relatively small patient population was included in our study compared to the literature. Thirdly, spleen and constitutional symptoms responses were evaluated with physicians’ reports. Ultrasonography was also used for imaging the spleen response in many centers. But this technique was not routinely used for evaluating spleen response in studies. In conclusion, ruxolitinib is a safe and effective therapy in Turkish patients with MF. Indeed lower initial ruxolitinib doses were associated with lower dose modification rate; spleen response might be affected by lower ruxolitinib doses. We can conclude that ruxolitinib dose titration based on the current guidelines can provide better responses in terms of not only clinical benefit but also for long term of ruxolitinib treatment.This study was approved by Ege University Ethical Committee with a number of 16-6.1/9.