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Mohammad Z Haider,1 Amna Al-Mannai,1 Sally Al-Sirhan,1 Ahmed Elsabagh,1 Nasser Nasser,1 Noora Al-Quraishi,1 Amr Ouda,1 Khadija Erradi,1 Anas A Ashour,2 Ishita Gupta,1,3 Jazeel Abdulmajeed,4 Hamad E Al-Romaihi,4 Devendra Bansal,4 Omran AH Musa,4 Elmoubasher Abu Baker Abd Farag,4 Mohammed HJ Al-Thani,4 Ala-Eddin Al Moustafa1,3,5 1College of Medicine, QU Health, Qatar University, Doha, Qatar; 2Department of Internal Medicine, Hamad Medical Corporation, Doha, Qatar; 3Biomedical and Pharmaceutical Research Unit, QU Health, Qatar University, Doha, Qatar; 4Ministry of Public Health, Doha, Qatar; 5Biomedical Research Centre, Qatar University, Doha, QatarCorrespondence: Ala-Eddin Al Moustafa, College of Medicine, QU Health, Qatar University, PO Box 2713, Doha, Qatar, Tel +974 4403 7817, Fax +974 4403-3333, Email aalmoustafa@qu.edu.qaPurpose: Predisposition to acute illness from COVID-19 is suggested to correlate with cigarette smoking as it augments the risk of developing cardiovascular and respiratory illnesses, including infections. However, the effects of smoking on COVID-19 symptoms are not well described and controversial. In this study, we aim to explore the associations between smoking and COVID-19 symptoms.Subjects and Methods: A cross-sectional study using the Ministry of Public Health (MoPH), Qatar database was administered to a Qatari population with confirmed COVID-19 disease who filled in pre-defined phone-call questionnaire between 27th February 2020 and 31st December 2020. We analyzed 11,701 non-vaccinated COVID-19 individuals (2952 smokers and 8749 non-smokers) with confirmed RT-PCR test results. The association of smoking and the presence of symptoms as well as patient characteristics was calculated using Pearson’s Chi-square and Fisher’s exact tests, adjusting for potential covariates.Results: Compared with the non-smokers, symptomatic COVID-19 infection is significantly higher in smokers. In addition, we found fever as the most common symptom developed in COVID-19 patients followed by cough, headache, muscle ache, and sore throat. As compared to other symptoms, association of smoking with chills and abdominal pain was less evident (P < 0.05 and P < 0.001, respectively). However, both groups showed similar rates of developing cough.Conclusion: In conclusion, smoking is associated with COVID-19 symptoms frequency in non-vaccinated patients; nevertheless, further investigations are necessary to understand the mechanism of this association which could generate new targets for the management of COVID-19 in smoker patients.Keywords: COVID-19, smoking, frequency, Qatar, symptoms

Abstract: With emerging new drugs in myelofibrosis (MF), a robust and harmonized framework for defining the severity of anemia and response to treatment will enhance clinical investigation and facilitate interstudy comparisons. Accordingly, the lead authors on the 2013 edition of the International Working Group-European LeukemiaNet (IWG-ELN) response criteria in MF were summoned to revise their document with the intent to (1) account for gender-specific differences in determining hemoglobin levels for eligibility criteria; (2) revise the definition of transfusion-dependent anemia (TDA) based on current restrictive transfusion practices; and (3) provide a structurally simple and easy to apply response criteria that are sensitive enough to detect efficacy signals (minor response) and also account for major responses. The initial draft of the 2024 IWG-ELN proposed criteria was subsequently circulated around a wider group of international experts and their feedback incorporated. The proposed articles include new definitions for TDA (≥3 units in the 12 weeks before study enrollment) and hemoglobin thresholds for eligibility criteria (<10 g/dL for women and <11 g/dL for men). The revised document also provides separate (TDA vs non-TDA) and graded (major vs minor response) response criteria while preserving the requirement for a 12-week period of screening and observation on treatment., (© 2024 American Society of Hematology. Published by Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.)

Introduction: Some Janus kinase (JAK) inhibitors such as ruxolitinib and fedratinib do not address and may worsen anemia in patients with myelofibrosis. In these cases, the JAK inhibitor may be continued at a reduced dose in an effort to maintain splenic and symptom control, with supportive therapy and/or red blood cell (RBC) transfusions added to manage anemia. This post hoc descriptive analysis of the phase 3 SIMPLIFY-2 trial evaluated the relative benefits of this approach versus switching to the JAK1/JAK2/activin A receptor type 1 inhibitor momelotinib in patients for whom anemia management is a key consideration., Methods: SIMPLIFY-2 was a randomized (2:1), open-label, phase 3 trial of momelotinib versus best available therapy (BAT; 88.5% continued ruxolitinib) in JAK inhibitor-experienced patients with myelofibrosis (n = 156). Patient subgroups (n = 105 each) were defined by either baseline (1) hemoglobin (Hb) of < 100 g/L or (2) non-transfusion independence (not meeting the criteria of no transfusions and no Hb of < 80 g/L for the previous 12 weeks); outcomes have been summarized descriptively., Results: In both subgroups of interest, week 24 transfusion independence rates were higher with momelotinib versus BAT/ruxolitinib: baseline Hb of < 100 g/L, 22 (33.3%) versus 5 (12.8%); baseline non-transfusion independent, 25 (34.7%) versus 1 (3.0%). Mean Hb levels over time were also generally higher in both subgroups with momelotinib, despite median transfusion rates through week 24 with momelotinib being comparable to or lower than with BAT/ruxolitinib. Spleen and symptom response rates with momelotinib in these subgroups were comparable to the intent-to-treat population, while rates with BAT/ruxolitinib were lower., Conclusion: In patients with moderate-to-severe anemia and/or in need of RBC transfusions, outcomes were improved by switching to momelotinib rather than continuing ruxolitinib and using anemia supportive therapies., Trial Registration: ClinicalTrials.gov: NCT02101268., (© 2024. Crown.)

Backround: Real-world, long-term survival outcomes of neoadjuvant, docetaxel-based therapy for esophageal and junctional adenocarcinoma are lacking. This study describes the long-term survival outcomes of patients with esophageal and junctional adenocarcinoma treated with neoadjuvant docetaxel-based chemotherapy and en bloc transthoracic esophagectomy., Methods: A retrospective cohort analysis of a prospectively maintained database from a regional upper gastrointestinal cancer network in Quebec, Canada, was performed. From January 2007 to December 2021, all patients with locally advanced (cT3 and/or N1) esophageal/Siewert I/II adenocarcinoma treated with neoadjuvant DCFx3 (Docetaxel/Cisplatin/5FU) or FLOTx4 (5FU/Leucovorin/Oxaliplatin/Docetaxel) and transthoracic en bloc esophagectomy were identified. Postoperative, pathological, and survival outcomes were compared., Results: Overall, 236 of 420 patients met the inclusion criteria. Tumor location was esophageal/Siewert I/Siewert II (118/33/85), most were cT3-4 (93.6%) and cN+ (61.0%). DCF and FLOT were used in 127 of 236 (53.8%) and 109 of 236 (46.2%). All neoadjuvant cycles were completed in 87.3% with no difference between the regimens. Operative procedures included Ivor Lewis (81.8%), left thoraco-abdominal esophagectomy (10.6%) and McKeown (7.6%) with an R0 resection in 95.3% and pathological complete response in 9.7% (DCF 12.6%/FLOT 6.4%, p = 0.111). The median lymph node yield was 32 (range 4-79), and 60.6% were ypN+. Median follow-up was longer for the DCF group (74.8 months 95% confidence interval [CI] 4-173 vs. 37.8 months 95% CI 2-119, p <0.001. Overall survival was similar between the groups (FLOT 97.3 months, 78.6-115.8 vs. DCF 92.9, 9.2-106.5, p = 0.420)., Conclusions: Neoadjuvant DCF and FLOT followed by transthoracic en bloc resection are both highly effective regimens for locally advanced esophageal adenocarcinoma with equivalent survival outcomes despite high disease load., (© 2023. Society of Surgical Oncology.)

Myeloproliferative neoplasms (MPNs) are a group of chronic hematologic malignancies that lead to morbidity and early mortality due to thrombotic complications and progression to acute leukemia. Clinical and mutational risk factors have been demonstrated to predict outcomes in patients with MPNs and are used commonly to guide therapeutic decisions, including allogenic stem cell transplant, in myelofibrosis. Adolescents and young adults (AYA, age ≤45 years) comprise less than 10% of all MPN patients and have unique clinical and therapeutic considerations. The prevalence and clinical impact of somatic mutations implicated in myeloid disease has not been extensively examined in this population. We conducted a retrospective review of patients evaluated at eight Canadian centers for MPN patients diagnosed at ≤45 years of age. In total, 609 patients were included in the study, with median overall survival of 36.8 years. Diagnosis of prefibrotic or overt PMF is associated with the lowest OS and highest risk of AP/BP transformation. Thrombotic complications (24%), including splanchnic circulation thrombosis (9%), were frequent in the cohort. Mutations in addition to those in JAK2/MPL/CALR are uncommon in the initial disease phase in our AYA population (12%); but our data indicate they may be predictive of transformation to post-ET/PV myelofibrosis., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: Posterior cerebral circulation ischemic stroke (PCS) comprises up to 25% of all strokes. It is characterized by variable presentation, leading to misdiagnosis and morbidity and mortality. We aim to describe PCS in large multiethnic cohorts., Methods: A retrospective review of a large national stroke database from its inception on the 1st of January 2014 till 31 December 2020. Incidence per 100,000 adult population/year, demographics, clinical features, stroke location, and outcomes were retrieved. We divided the cohort into patients from MENA (Middle East and North Africa) and others., Results: In total, 1,571 patients were identified. The incidence of PCS was observed to be rising and ranged from 6.3 to 13.2/100,000 adult population over the study period. Men were 82.4% of the total. The mean age was 54.9 ± 12.7 years (median 54 years, IQR 46, 63). MENA patients comprised 616 (39.2%) while others were 954 (60.7%); of these, the majority (80.5%) were from South Asia. Vascular risk factors were prevalent with 1,230 (78.3%) having hypertension, 970 (61.7%) with diabetes, and 872 (55.5%) having dyslipidemia. Weakness (944, 58.8%), dizziness (801, 50.5%), and slurred speech (584, 36.2%) were the most commonly presenting symptoms. The mean National Institute of Health Stroke Score (NIHSS) score was 3.8 ± 4.6 (median 3, IQR 1, 5). The overall most frequent stroke location was the distal location (568, 36.2%). The non-MENA cohort was younger, less vascularly burdened, and had more frequent proximal stroke location ( p  < 0.05). Dependency or death at discharge was seen in 39.5% and was associated with increasing age, and proximal and multilocation involvement; while at 90 days it was 27.4% and was associated with age, male sex, and having a MENA nationality ( p  < 0.05)., Conclusion: In a multiethnic cohort of posterior circulation stroke patients from the MENA region and South Asia, we noted a rising incidence over time, high prevalence of vascular risk factors, and poor outcomes in older men from the MENA region. We also uncovered considerable disparities between the MENA and non-MENA groups in stroke location and outcome. These disparities are crucial factors to consider when tailoring individualized patient care plans. Further research is needed to thoroughly investigate the underlying reasons for these variations., Competing Interests: 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., (Copyright © 2024 Imam, Chandra, Singh, Hakeem, Al Sirhan, Kotob, Akhtar, Kamran, Al Jerdi, Muhammad, Haroon, Hussain, Perkins, Elalamy, Alhatou, Ali, Abdelmoneim, Joseph, Morgan, Uy, Bhutta, Azad, Ayyad, Elsotouhy, Own and Deleu.)

Allogeneic hematopoietic cell transplantation (HCT) is the only curative therapy for myelofibrosis (MF) and is recommended for patients with higher risk disease. However, there is a risk of early mortality, and optimal timing is unknown. JAK inhibitor (JAKi) therapy may offer durable improvement in symptoms, splenomegaly and quality of life. The aim of this multicentre, retrospective observational study was to compare outcomes of patients aged 70 years or below with MF in chronic phase who received upfront JAKi therapy vs. upfront HCT in dynamic international prognostic scoring system (DIPSS)-stratified categories. For the whole study cohort, median overall survival (OS) was longer for patients who received a JAKi vs. upfront HCT, 69 (95% CI 57-89) vs. 42 (95% CI 20-not reached, NR) months, respectively (p = 0.01). In patients with intermediate-2 and high-risk disease, median OS was 55 (95% CI 36-73) months with JAKi vs. 36 (95% CI 20-NR) months for HCT (p = 0.27). An upfront HCT strategy was associated with early mortality and difference in median OS was not observed in any risk group by 5 years of follow-up. Within the limitations of a retrospective observational study, we did not observe any benefit of a universal upfront HCT approach for higher-risk MF., (© 2023. The Author(s).)

Objectives: Haematology patients are more likely to receive high intensity care near end of life (EOL) than patients with solid malignancy. Previous authors have suggested indicators of quality EOL for haematology patients, based on a solid oncology model. We conducted a retrospective chart review with the objectives of (1) determining our performance on these quality EOL indicators, (2) describing the timing of level of intervention (LOI) discussion and palliative care (PC) consultation prior to death and (3) evaluating whether goals of therapy (GOT), PC consultation and earlier LOI discussion are predictors of quality EOL., Methods: We identified patients who died from haematological malignancies between April 2014 and March 2016 (n=319) at four participating McGill University hospitals and performed retrospective chart reviews., Results: We found that 17% of patients were administered chemotherapy less than 14 days prior to death, 20% of patients were admitted to intensive care, 14% were intubated and 5% were resuscitated less than 30 days prior to death, 18% of patients received blood transfusion less than 7 days prior to death and 67% of patients died in an acute care setting. LOI discussion and PC consultation occurred a median of 22 days (IQR 7-103) and 9 days (IQR 3-19) before death. Patients with non-curative GOT, PC consultation or discussed LOI were significantly less likely to have high intensity EOL outcomes., Conclusions: In this study, we demonstrate that LOI discussions, PC consults and physician established GOT are associated with quality EOL outcomes for patients with haematological malignancies., Competing Interests: Competing interests: TM is a board member of the International papilloma virus society. SS has received research support from Novartis, has sat on the scientific advisory board for Novartis and BMS-Celgene, and has acted as a consultant for Novartis, BMS-Celgene, Sierra Oncology, Constellation, Janssen, Astrazeneca, Abbvie and GSK. KD has acted as a consultant for Abbvie, Kite, Roche, Seagen, Novartis, BMS, Janssen and Beigene and has received honoraria from Incyte. SA has received research support from Novartis and has acted as a consultant and received honoraria from Palladin, Roche, Novartis, BMS, Janssen, Astra Zeneca and Pfizer., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Intramuscularly administered vaccines stimulate robust serum neutralizing antibodies, yet they are often less competent in eliciting sustainable "sterilizing immunity" at the mucosal level. Our study uncovers a strong temporary neutralizing mucosal component of immunity, emanating from intramuscular administration of an mRNA vaccine. We show that saliva of BNT162b2 vaccinees contains temporary IgA targeting the receptor-binding domain (RBD) of severe acute respiratory syndrome coronavirus-2 spike protein and demonstrate that these IgAs mediate neutralization. RBD-targeting IgAs were found to associate with the secretory component, indicating their bona fide transcytotic origin and their polymeric multivalent nature. The mechanistic understanding of the high neutralizing activity provided by mucosal IgA, acting at the first line of defense, will advance vaccination design and surveillance principles and may point to novel treatment approaches and new routes of vaccine administration and boosting., Competing Interests: Hebrew University of Jerusalem, Hadassah-Hebrew University Medical Center and Hadassah Academic College has filed a patent application “Compounds and methods for increasing antibody’s neutralization properties and methods for assessing antibody response” on which MSR, SuK, AF, PG, RW, DP, LB, and AR are listed as inventors. 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., (Copyright © 2023 Stolovich-Rain, Kumari, Friedman, Kirillov, Socol, Billan, Pal, Das, Golding, Oiknine-Djian, Sirhan, Sagie, Cohen-Kfir, Gold, Fahoum, Kumar, Elgrably-Weiss, Zhou, Ravins, Gatt, Bhattacharya, Zelig, Wiener, Wolf, Elinav, Strahilevitz, Padawer, Baraz and Rouvinski.)

Background: Calcium and iron are crucial essential minerals. Iron is mainly responsible for transporting oxygen in the body and the immune system. In comparison, calcium's primary function is in human bones and teeth. Due to that, it is vital to quantify the amount in vegetables., Objective: Optimization and validation of three analytical procedures, visible, atomic emission spectrophotometry (AES), and atomic absorption spectrophotometry (AAS), were developed to determine calcium and iron in vegetables and wastewater samples using response surface methodology (RSM) via Box-Behnken design (BBD). The design helps to reduce experiment trials with selected variables to find a correlation between them and their respective dependent variables., Methods: Method I was developed to quantify calcium in vegetables mixed with concentrated 3M HNO3 and heated to reflux as per the BBD. Then it was cooled, filtered, and completed with 3M HNO3 to be carried out utilizing AES and AAS. For method II, vegetables were mixed with nitric acid and sulfuric acid solution with an optimized 5M KSCN solution, which was computed using the AAS and visible spectrophotometry., Results: First, percentage of water content was calculated for all vegetables, higher in malabar spinach and lower in peas. The calcium and iron contents were present within 0.59-2.68 mg and 35.8-211.5 mg, respectively, in 100 g of vegetables. The results showed a higher amount of iron was available in spinach and a lower amount in okra. In contrast, the highest calcium amount was present in broccoli and the lowest amount was in peas. The calcium and iron content were between 0.015-137.25 and 0.01-147.85 µg/mL in the wastewater samples., Conclusions: These methods can help to determine the amount of calcium and iron for the quality control samples in research and development, food, and the environmental industry., Highlights: Three validated analytical techniques quantify calcium and iron in vegetables and wastewater samples. The RSM-BBD optimized the method and determined its crucial factors., (© The Author(s) 2022. Published by Oxford University Press on behalf of AOAC INTERNATIONAL. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: The COVID-19 pandemic has transformed and affected every aspect of health care. Like any catastrophic event, the stress on hospitals to maintain a certain level of function is immense. Acute surgical pathologies cannot be prevented or curtailed; therefore, it is important to understand patterns and outcomes during catastrophes in order to optimize care and organize the health care system., Methods: In a single urban tertiary care center, a retrospective study examined the first complete lockdown period of Israel during the COVID-19 pandemic. This was compared to the same time period the previous year., Results: During the pandemic, time to hospitalization was significantly decreased. There was also an overall reduction in surgical admissions yet with a higher percentage being hospitalized for further treatment (69.2% vs 23.5%). The patients admitted during this time had a higher APACHE-II score and Charlson comorbidity index score. During the pandemic, time to surgery was decreased, there were less laparoscopic procedures, and more RBC units were used per patient. There were no differences in overall complications, except when sub-analyzed for major complications (9.7% vs 6.3%). There was no significant difference in overall in-house mortality or morbidity. Length of hospitalization was significantly decreased in the elderly population during the pandemic., Conclusion: During the COVID-19 pandemic, despite a significantly less number of patients presenting to the hospital, there was a higher percentage of those admitted needing surgical intervention, and they were overall sicker than the previous year.

Recently discovered SARS-CoV-2 caused a pandemic that triggered researchers worldwide to focus their research on all aspects of this new peril to humanity. However, in the absence of specific therapeutic intervention, some preventive strategies and supportive treatment minimize the viral transmission as studied by some factors such as basic reproduction number, case fatality rate, and incubation period in the epidemiology of viral diseases. This review briefly discusses coronaviruses' life cycle of SARS-CoV-2 in a human host cell and preventive strategies at some selected source of infection. The antiviral activities of synthetic and natural polymers such as chitosan, hydrophobically modified chitosan, galactosylated chitosan, amine-based dendrimers, cyclodextrin, carrageenans, polyethyleneimine, nanoparticles are highlighted in this article. Mechanism of virus inhibition, detection and diagnosis are also presented. It also suggests that polymeric materials and nanoparticles can be effective as potential inhibitors and immunization against coronaviruses which would further develop new technologies in the field of polymer and nanoscience., (© The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2021.)

There is an increasing demand for sustainable and safe packaging technologies to improve consumer satisfaction, reduce food loss during storage and transportation, and track the quality status of food throughout its distribution. This study reports the fabrication of colorimetric pH-indicative and flame-retardant nanocomposite films (NCFs) based on polyvinyl alcohol (PVA) and nanoclays for smart and safe food packaging applications. Tough, flexible, and transparent NCFs were obtained using 15% nanoclay loading (PVA-15) with superior properties, including low solubility/swelling in water and high thermal stability with flame-retardant behavior. The NCFs showed average mechanical properties that are comparable to commercial films for packaging applications. The color parameters were recorded at different pH values and the prepared NCFs showed distinctive colorimetric pH-responsive behavior during the transition from acidic to alkaline medium with high values for the calculated color difference (∆E ≈ 50). The prepared NCFs provided an effective way to detect the spoilage of the shrimp samples via monitoring the color change of the NCFs during the storage period. The current study proposes the prepared NCFs as renewable candidates for smart food packaging featuring colorimetric pH-sensing for monitoring food freshness as well as a safer alternative choice for applications that demand films with fire-retardant properties.

Nowadays, integrated microfiltration (MF) membrane systems treatment is becoming widely popular due to its feasibility, process reliability, commercial availability, modularity, relative insensitivity in case of wastewater of various industrial sources as well as raw water treatment and lower operating costs. The well thought out, designed and implemented use of membranes can decrease capital cost, reduce chemical usage, and require little maintenance. Due to their resistance to extreme operating conditions and cleaning protocols, ceramic MF membranes are gradually becoming more employed in the drinking water and wastewater treatment industries when compared with organic and polymeric membranes. Regardless of their many advantages, during continuous operation these membranes are susceptible to a fouling process that can be detrimental for successful and continuous plant operations. Chemical and microbial agents including suspended particles, organic matter particulates, microorganisms and heavy metals mainly contribute to fouling, a complex multifactorial phenomenon. Several strategies, such as chemical cleaning protocols, turbulence promoters and backwashing with air or liquids are currently used in the industry, mainly focusing around early prevention and treatment, so that the separation efficiency of MF membranes will not decrease over time. Other strategies include combining coagulation with either inorganic or organic coagulants, with membrane treatment which can potentially enhance pollutants retention and reduce membrane fouling.

Ruxolitinib improves splenomegaly and other disease-related symptoms in patients with myelofibrosis, but over time, many patients lose this benefit. It is difficult to determine whether this is due to resistance or intolerance to the drug; thus, we have used the more inclusive term of ruxolitinib failure. The survival of patients with myelofibrosis after ruxolitinib failure is poor but varies significantly by the pattern of the failure, underlining the need for a clinically appropriate classification. In this review, we propose diagnostic guidance for early recognition of the pattern of ruxolitinib failure and we recommend treatment options. The most frequent patterns of ruxolitinib failure are loss or failure to obtain a significant reduction in splenomegaly or symptom response, and the development or persistence of clinically significant cytopenias. Ruxolitinib dose modification and other ancillary therapies are sometimes helpful, and splenectomy is a palliative option in selected cases. Stem-cell transplantation is the only curative option for these patterns of failure, but its restricted applicability due to toxicity highlights the importance of ongoing clinical trials in this area. Recent approval of fedratinib by the US Food and Drug Administration provides an alternative option for patients with suboptimal or loss of spleen response. The transformation of myelofibrosis to accelerated or blast phase is an infrequent form of failure with an extremely poor prognosis, whereby patients who are ineligible for transplantation have limited treatment options.

Purpose: A multidisciplinary team (MDT) approach to cancer management is gold-standard. With an increasing disease incidence and growing research into human papillomavirus (HPV)-related oropharyngeal cancer (OPC), updated UK management guidelines were recently published. This study aimed to evaluate the MDT decision-making process among OPC patients at a tertiary centre., Methods: MDT meetings over a 12-month period were analysed retrospectively. MDT decisions were compared with guidelines and patient records examined to identify decision implementation. Reasons behind any discordant decisions were explored., Results: This study included 140 OPC patients. Thirty-three (23.6%) were not tested for HPV. Patients over 70 years with a smoking history treated palliatively were less likely to be tested (P = 0.017). Eighty-five percent of MDT decisions followed guidelines with the majority not complying (76.2%) related to patient comorbidity. Ten decisions (7.1%) were not implemented. Reasons included: Seven due to patient choice, of which four patients (57.1%) were only seen following the MDT meeting, and three due to clinician decisions as new clinical information emerged., Conclusion: The majority of MDT decisions followed guidelines and any discordant decisions were justifiable. Discussing management options with patients beforehand facilitates decision implementation as decisions can potentially change after seeing the patient. Progress is still needed with regards to HPV testing. Reasons for not testing could include subliminal decision-making among clinicians, and patients falling between centres. Crucially, the role of the MDT in head and neck cancer should be to ratify decisions rather than making them, hence the need to see patients prior to MDT discussion.

Objective: To document the Mayo Clinic decades-long experience with myeloproliferative neoplasms (MPNs) and provide mature risk-stratified survival data and disease complication estimates., Patients and Methods: All Mayo Clinic patients with World Health Organization-defined MPNs constituted the core study group and included those with polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF)., Results: A total of 3023 consecutive patients (median age, 62 years; range, 18-96 years) were considered: 665 PV, 1076 ET, and 1282 PMF. From October 27, 1967, through December 29, 2017, 1631 deaths (54%), 183 leukemic transformations (6%), 244 fibrotic progressions (14%), and 516 thrombotic events (17%) were recorded. Median overall survival (OS) was 18 years for ET, 15 years for PV, and 4.4 years for PMF (P<.05 for all intergroup comparisons). Inferior survival was documented in patients with ET diagnosed more recently (post-1990) (P<.001), whereas survival data were time independent in PV and PMF. After conventional risk stratification, OS in low-risk ET and low-risk PV were superimposed (P=.89) but each differed significantly from that of age- and sex-matched controls (P<.001). Leukemia-free survival was similar for ET and PV (P=.22) and significantly worse with PMF (P<.001). Compared with ET, PV was associated with higher risk of fibrotic progression (P<.001). Thrombosis risk after diagnosis was highest in PV and lowest in PMF (P=.002 for PV vs ET; P=.56 for ET vs PMF; and P=.001 for PV vs PMF)., Conclusion: This study provides the most mature survival and outcomes data in MPNs and highlights MPN subgroup risk categorization as key in appraising disease natural history. The OS was only marginally better in ET compared with PV, and PV displayed a higher risk of thrombosis and fibrotic progression., (Copyright © 2018 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

Momelotinib, a small-molecule inhibitor of Janus kinase 1 and Janus kinase 2, has demonstrated efficacy in myelofibrosis patients with 300 mg, once-daily dosing. This open-label, non-randomized, phase 1/2 study evaluated the safety and therapeutic benefit of momelotinib with twice-daily dosing. A total of 61 subjects with primary myelofibrosis or post-polycythemia vera/post-essential thrombocythemia myelofibrosis with intermediate- or high-risk disease received momelotinib. A phase 1 dose escalation identified 200 mg twice daily as the optimal dose to be expanded in phase 2. The most frequent adverse events were diarrhea (45.9%), peripheral neuropathy (44.3%), thrombocytopenia (39.3%), and dizziness (36.1%), the latter primarily due to a first-dose effect. The response assessment according to the 2006 International Working Group criteria (≥8 weeks duration at any time point) demonstrated spleen response by palpation of 72% (36/50) and anemia response of 45% (18/40). Spleen response by magnetic resonance imaging obtained at 24 weeks was 45.8% (27/59) for all subjects and 54.0% (27/50) for those with palpable splenomegaly at baseline. The symptoms of myelofibrosis were improved in most subjects. Cytokine analysis showed a rapid decline in interleukin-6 with momelotinib treatment, and a slower reduction in other inflammatory cytokines. In the subgroup of subjects with the JAK2V617F mutation at baseline (n=41), momelotinib significantly reduced the allele burden by 21.1% (median) at 24 weeks. These results provide evidence of tolerability and a potential therapeutic activity of momelotinib for subjects that support further evaluation in ongoing, phase 3 randomized trials. (clinicaltrials. gov identifier:01423058)., (Copyright© Ferrata Storti Foundation.)

Objectives: The aim of this study was to evaluate the antimicrobial effect of cold plasma (CP) on infected dentin surfaces in vitro and ex vivo., Materials and Methods: To examine the effect of cold plasma on root surfaces, 24 root surfaces were infected with Streptococcus mitis. Specimens were randomly divided into three groups: Within the control group (C), root surfaces were rinsed with NaCl; root surfaces in the second group were additionally scaled and root planed (SRP), and in the third group, root surfaces were rinsed, scaled, root planed, and in addition, CP was applied (SRP + CP). To examine the effect of CP on root caries lesions (RCLs), 16 freshly extracted teeth with symmetrical carious lesions were equally divided into two groups. In the control group, carious lesions were treated with chlorhexidine (CHX), whereas CHX was applied in conjunction with CP in the test group (CHX + CP). For microbiological analysis, dentin samples were serially diluted and CFU counts were estimated after 24 h of incubation., Results: Compared to C, mean CFU values for SRP and SRP + CP were significantly lower (p < 0.05). In addition, mean CFUs for SRP + CP were reduced to 0 and, therefore, significantly lower than SRP (2.98 log CFU/mL) alone (p = 0.000, Mann-Whitney U). Regarding RCLs, significantly lower mean CFU values were observed for CHX + CP when compared to CHX (4.45 vs. 2.67 log CFU/mL, p = 0.002, Mann-Whitney U test)., Conclusions: For disinfection of exposed root surfaces, the adjunctive application of CP is promising. In addition, the combined application of CHX + CP has the potential to disinfect root dentin surfaces., Clinical Relevance: It was shown that the combination of cold plasma with CHX is the best available option for the disinfection of root surfaces.

Objectives: To standardize diagnostic investigations for myeloproliferative neoplasms (MPNs) to increase homogeneity in patient care and to streamline diagnostic approaches in the most efficient and cost-effective manner., Methods: The development of Canadian expert consensus recommendations for the diagnosis of MPNs began with a review of the following: clinical evidence, daily practice, existing treatment guidelines, and availability of diagnostic tools. Each group member was assigned a specific topic, which they discussed with the entire group during several consensus meetings., Results: This document provides the Canadian MPN group's recommendations, proposed diagnostic algorithms, and background evidence upon which decisions were made., Conclusions: Standardization of diagnostic investigations will increase homogeneity in patient care and provide a foundation for future clinical research in this rapidly evolving therapeutic area. Streamlining diagnostic approaches in the most efficient and cost-effective manner will also result in significant cost saving for the health care system., (© American Society for Clinical Pathology, 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Surface decontamination remains challenging in peri-implant infection therapy. To investigate the bactericidal efficacy of tissue tolerable plasma, S. mitis biofilms were created in vitro on 32 microrough titanium dental implants. Biofilm imaging was performed by confocal laser scanning microscopy (CLSM) and scanning electron microscopy (SEM). The implants were either rinsed with 1% NaCl as negative control (C) or irradiated with a diode laser (DL) for 60 sec as positive control or plasma (TTP60, TTP120) for 60 or 120 sec. Subsequently, colony forming units (CFU) were counted. Post-treatment, implants were further examined using fluorescence microscopy (FM). Median CFU counts differed significantly between TTP60, TTP120 and C (2.19 and 2.2 vs. 3.29 log CFU/ml; p = 0.012 and 0.024). No significant difference was found between TTP60 and TTP120 (p = 0.958). Logarithmic reduction factors were (TTP60) 2.21, (TTP120) 1.93 and (DL) 0.59. Prior to treatment, CLSM and SEM detected adhering bacteria. Post-treatment FM recorded that the number of dead cells was higher using TTP compared to DL and C. In view of TTP's effectiveness, regardless of resistance patterns and absence of surface alteration, its use in peri-implant infection therapy is promising. The results encourage conducting clinical studies to investigate its impact on relevant parameters., (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Objectives: Cold plasma (CP) has been shown to be effective even against multiresistant microorganisms. As previous investigations on the effect of CP in root canals showed promising results, the aim of the present study was to analyze the bactericidal efficacy of CP in different depths of infected dentin., Methods: 32 standardized root canals of human mandibular premolars were infected with Enterococcus faecalis and incubated for one week. Specimens were randomly selected for one of four disinfection methods: control (5mL NaCl), 5mL chlorhexidine (CHX), CP alone (CP), and a combination of 5mL CHX and cold plasma (CHX+CP). CHX was ultrasonically activated for 30s, while cold plasma was used for 60s in the root canals. Dentin samples at depths of 300, 500 and 800 µm were obtained and diluted serially. Colony forming units (CFUs) were counted on agar plates after 24h of incubation., Results: The highest overall logarithmic reduction factors (RF) were obtained from CHX+CP (log RF 3.56 p<0.01; Mann-Whitney U test), followed by CP (log RF 3.27 p<0.01) and CHX alone (log RF 2.65 p<0.01) related to the control. All disinfection methods showed significantly lower CFU counts compared to the control group in 300 µm and 800 µm (both p<0.01, Kruskal-Wallis test)., Discussion: The adjuvant use of CP might be beneficial in highly infected root canals to improved disinfection. However, the disinfection effect against Enterococcus faecalis of CP is comparable to ultrasonically activated CHX.

Polycythemia vera (PV) is a clonal stem cell disorder characterized by erythrocytosis and associated with burdensome symptoms, reduced quality of life, risk of thrombohemorrhagic complications, and risk of transformation to myelofibrosis and acute myeloid leukemia. The discovery of the JAK2 V617 mutation marked a significant milestone in understanding the pathophysiology of the disease and subsequently the diagnostic and therapeutic approaches. The current diagnostic criteria for PV are based on hemoglobin level and presence of the JAK2 V617 mutation. The treatment is geared toward prevention of thrombotic events, normalization of blood counts, control of disease-related symptoms, and potential prolongation of survival. Cytoreductive therapy is indicated in patients at increased risk of thrombosis. Hydroxyurea (HU) remains the most commonly used first-line cytoreductive therapy and is superior to phlebotomy in reducing risk of arterial and venous thrombosis. Interferon (IFN) is used either at failure of HU or in selected patients as first-line therapy. The results of pegylated IFN in phase 2 studies appear encouraging, with molecular responses occurring in some patients. Ongoing phase 3 studies of HU versus pegylated IFN will define the optimal first-line cytoreductive therapy for PV. A recent phase 3 trial has shown the superiority of the JAK1/2 inhibitor ruxolitinib in comparison to best available treatment in HU-intolerant or -resistant patients. The therapeutic landscape of PV is likely to change in the near future. In this report, we assess the potential impact of the changing landscape of PV management on daily practice., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Percutaneous thoracic interventions are among the most common procedures in today's medical practice. From the simple placement of a pleural drain to the ablation of lung tumors, the advent of image guidance has revolutionized minimally invasive procedures and has allowed for the introduction of new techniques and widened the range of indications. It is therefore imperative to understand the complications associated with these interventions and their management. This article illustrates the common complications associated with these interventions and highlights the relative safety of these interventions.

Objective: The number of older people is growing fast in Turkey. In this context, internal medicine residents and specialists contact older people more frequently. Thus, healthcare providers' knowledge and attitudes toward older people is becoming more important. Studies that specifically investigate internal medicine residents' attitudes toward the elderly are scarce. We aimed to investigate the attitudes of internal medicine residents toward older people., Methods: This cross-sectional multicenter study was undertaken in the internal medicine clinics of six university state hospitals that provide education in geriatric care. All internal medicine residents working in these hospitals were invited to participate in this questionnaire study between March 2013 and December 2013. We recorded the participants' age, sex, duration of internal medicine residency, existence of relatives older than 65 years, history of geriatrics course in medical school, geriatrics rotation in internal medicine residency, and nursing home visits., Results: A total of 274 (82.3%) of the residents participated in this study, and 83.6% of them had positive attitudes toward older people. A geriatrics rotation during internal medicine residency was the only independent factor associated with positive attitudes toward the elderly in this multivariate analysis. A geriatrics course during medical school was associated with positive attitudes in the univariate analysis, but only tended to be so in the multivariate analysis., Conclusion: Geriatrics rotation during internal medicine residency was independently associated with positive attitudes toward older people. Generalization of geriatrics education in developing countries may translate into a better understanding and improved care for older patients., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Myelofibrosis (MF) is a clonal stem cell disorder characterized by cytopenias, splenomegaly, marrow fibrosis, and systemic symptoms due to elevated inflammatory cytokines. MF is associated with decreased survival. The quality of life of patients with MF is similar to other advanced malignancies. Allogeneic hematopoietic cell transplantation is a curative treatment, but is applicable to a minority of patients with MF. None of the conventional therapies are known to alter the natural history of the disease. Significant progress has been made in the last few years in the understanding of disease biology of MF. Discovery of the JAK2V617F mutation paved the way for drug discovery in MF, and the first JAK1/2 inhibitor, ruxolitinib, has been approved by FDA and Health Canada. Several other JAK1/2 inhibitors are at various stages of clinical development. As a consequence, the therapeutic landscape of MF is changing from a disease where no effective therapies existed to one with several novel treatment options on the horizon. In this report, we assess the changing therapeutic options for MF, and critically analyze the position of novel treatments in the current armamentarium.

Comparative genomic hybridization (CGH), using oligo arrays with either 44,000 or 105,000 oligonucleotides, was performed on granulocyte-derived DNA from 71 patients with BCR-ABL-negative classic myeloproliferative neoplasms (MPNs): 32 primary myelofibrosis (PMF), 26 polycythemia vera (PV) and 13 essential thrombocythemia (ET). Copy number changes (CNCs) were detected in 44%, 35%, and 15% of the cases with PMF, PV and ET, respectively. In ET and PMF, CNCs were more frequently detected in the presence of JAK2V617F (50% vs. 19%; p=0.05). Conventional chromosome analysis was obtained in 57 patients either at diagnosis or within 1 year of the array CGH study; all 21 patients with PV and 11 with ET displayed normal cytogenetic findings despite the presence of CNCs in 29% and 18%, respectively. In PMF, the respective rates of CNCs and abnormal karyotype were 48% and 36%; karyotypic abnormalities, including unbalanced translocations, were often detected by array CGH as chromosomal gains or losses. This preliminary report suggests a potential value for array CGH in terms of both clinical diagnostics and genomic research in MPNs.

JAK2V617F-positive patients with essential thrombocythemia, as opposed to their mutation-negative counterparts, require lower doses of hydroxyurea (HU) for control of their platelet count. In the current study, we looked for predictors of HU response in 69 patients with primary myelofibrosis (PMF) and 56 with polycythemia vera (PV). JAK2V617F analysis was performed on bone marrow-derived DNA obtained at or near the time of diagnosis. HU response in PMF was associated with a shorter disease duration (P = 0.008), absence of previous therapy (P = 0.01), older age at diagnosis (P = 0.009), and presence of JAK2V617F (P = 0.02). On multivariable analysis, only the latter retained its significance (48% vs. 8% response in mutation positive vs. negative cases). In PV, JAK2V617F allele burden correlated directly with HU response (P = 0.05) and inversely with daily HU dose in responding patients (P = 0.02). The current study suggests that JAK2V617F presence identifies PMF patients who are likely to respond to HU therapy, and information on its allele burden helps in assigning the optimal starting dose in individual patients with PV., (Copyright 2008 Wiley-Liss, Inc.)

Polycythaemia vera (PV) is closely associated with both an acquired activating mutation of the JAK2 tyrosine kinase (JAK2(V617F)) in granulocyte-derived DNA and increased granulocyte polycythaemia rubra vera-1 (PRV-1) expression. In order to explore the correlation between these two biological markers and compare their diagnostic utility, mutation analysis for JAK2(V617F) and quantitative measurement of granulocyte PRV-1 expression were performed on the same study sample from 100 participants: 38 with PV, 22 with essential thrombocythaemia (ET), 10 with agnogenic myeloid metaplasia (AMM), 19 with secondary polycythaemia (SP) and 11 healthy volunteers. The respective overall (homozygous) JAK2(V617F) mutational frequencies were 95% (26%), 55% (0%), 30% (0%), 0% and 0%. The corresponding figures for increased PRV-1 expression were 89%, 18%, 20%, 21% and 9%. In patients with either ET or AMM, the likelihood of detecting JAK2(V617F) was significantly higher in the presence of an increased PRV-1 expression (83% vs. 38%; P = 0.05). Similarly, in patients with PV, homozygous as compared with heterozygous JAK2(V617F) correlated with higher levels of PRV-1 expression (P = 0.11). The present study suggests an allele dose-dependent effect of JAK2(V617F) on granulocyte PRV-1 expression. However, compared with the PRV-1 assay, mutation screening for JAK2(V617F) displayed greater accuracy in distinguishing PV from SP.

Background: Despite the absence of any systematic evidence for diagnostic utility, red cell mass (RCM) measurement has been endorsed as a major diagnostic criterion for polycythemia vera (PV) based on a set of eligibility criteria for a clinical trial formulated by an International PV Study Group in 1967., Methods: A retrospective analysis was performed on a consecutive series of 105 patients who underwent blood volume measurements for evaluation of polycythemia. In a previous study, the authors had systematically compared RCM measurement by 51Cr-labeled erythrocytes and 125I-labeled human serum albumin and demonstrated equivalence between the two methods. In the current study, they used the latter method and applied the International Committee for Standardization in Haematology recommendations for result interpretation in order to evaluate test performance and practical utility., Results: RCM exceeded the 98-99% limits of the reference range in 76%, 20%, 22%, and 57% of patients with PV (n = 25), secondary polycythemia (n = 35), spurious or apparent polycythemia (n = 38), and essential thrombocythemia (n = 7), respectively. Decreased plasma volume was rarely seen in any of the disease categories. In all instances of PV, the diagnosis was readily apparent, based on alternative clinical and laboratory tests, and did not require the additional information from blood volume measurement. Furthermore, alternative methods of PV diagnosis, based on disease-specific biological markers as well as bone marrow histology, are now available., Conclusions: The continued use of RCM and plasma volume measurements for the diagnosis of PV is no longer warranted.

In a prospective study, peripheral blood (PB) CD34 count, bone marrow histology and other clinical parameters were concurrently evaluated in 94 patients with myelofibrosis with myeloid metaplasia (MMM) and the study cohort followed for a minimum of 3 years. Median PB CD34 count was 0.0547 x 10(9)/l (range 0-5.345 x 10(9)/l) with 86% of the patients displaying above normal levels (>0.005 x 10(9)/l). In a multivariate analysis, only leucocyte count and PB blast percentage correlated with PB CD34 count in an independent and consistent fashion. After a median follow up of 41 months from PB CD34 analysis, 43 patients (46%) have died with a projected 5-year survival of 50%. In a univariate analysis, PB CD34 count above 0.1 x 10(9)/l correlated significantly with shortened survival, leukaemic transformation and clinical progression. However, such statistical significance was lost during multivariate analysis, which identified only anaemia and leucocytosis as independent risk factors for shortened survival. Furthermore, sequential analysis of PB CD34 count was performed in 53 patients and 43% of those who progressed clinically did not display a concomitant rise in their PB CD34 count. The current prospective study does not support an independent prognostic value for PB CD34 count in MMM.

Inherited C3 deficiency may result from mutations in the C3 gene affecting transcription or translation (type I deficiency). We described a type II C3 deficiency caused by a mutation yielding an abnormal non-secreted C3. The post-translational processing of mutant and normal C3 was analyzed in fibroblasts grown from skin biopsies. Mutant C3 is located mainly in the endoplasmic reticulum (ER), whereas normal C3 is seen evenly distributed throughout the cytoplasm. Most of the mutant C3 is degraded within the cell, and only a small fraction (around 8%) is secreted after 20 h chase. Processing of C3 at 19 degrees C was reduced in normal fibroblasts but completely blocked in mutant fibroblasts. ATP depletion blocked processing of normal proC3 to C3. In contrast, the mutant proC3 was partly degraded in ATP-depleted cells, yet its complete degradation and secretion were blocked. Intracellular degradation of the mutant C3 was not inhibited by NH4Cl, thus excluding cleavage within lysosomes. These results demonstrate that the type II mutant C3 studied here is retained in the ER probably by a quality contol machinery that identifies abnormal protein folding. Consequently, it is destined to undergo a two-step intracellular degradation; an initial ATP-independent step followed by an ATP-dependent step.