Recipient selection for liver transplantation in hepatocellular carcinoma (HCC) is based primarily on criteria affecting the chance of long-term success. Here, the relationship between pretransplant bridging therapy and long-term survival was investigated in a subgroup analysis of the SiLVER Study.versus progressive disease (more than 20 per cent tumour growth or development of new lesions).Response to bridging, as defined by comparison of imaging at the time of listing and post-transplant pathology report, was categorized into controlled P = 0.005). For patients within the Milan criteria (MC) at listing, mean overall survival was longer for those with controlled versus progressive disease . Importantly, patients with HCCs outside the MC that were downsized to within the MC before liver transplantation had poor outcomes compared with patients who never exceeded the MC .Of 525 patients with HCC who had liver transplantation, 350 recipients underwent pretransplant bridging therapy. Tumour progression despite bridging was an independent risk factor affecting overall survival (hazard ratio 1.80; Patients with HCCs within the MC that did not show tumour progression under locoregional therapy had the best outcomes after liver transplantation. Downstaging into the limits of the MC did not improve the probability of survival.Prognostic factors determining the long-term success of liver transplantation in patients with hepatocellular carcinoma are still under discussion. A subgroup analysis of the SiLVER trial showed that disease control under bridging therapy is strongly associated with improved prognosis in terms of overall survival. However, in tumours exceeding the limits of the Milan criteria, downstaging did not restore the probability of survival compared with that of patients within the Milan criteria. In this regard, many patients with HCC on the waiting list for LTx undergo routine locoregional treat-and-wait testing, which may be regarded as an Data from the SiLVER study  were used as a basis for this analysisP < 0.050 was considered statistically significant.Continuous data are shown as mean(s.d.). The probability of survival was modelled by Kaplan–Meier analysis, with differences evaluated using the log rank test, and Cox regression analysis in SPSS version 25 . Two-tailed Table 1). Mean(s.d.) age of the cohort was 57.8(7.0 years), and most of the study subjects were men (87.7 per cent). Mean time on the waiting list was 222 days, with a maximum of 7.25 years. Most tumours were smaller than 3 cm (58.3 per cent at time of listing), with the majority of the patients (51.7 per cent) presenting with single lesions. Approximately two-thirds of the patients had HCCs within the MC at the time of listing  and transplantation .Of 525 patients in the SiLVER study, 350 underwent one or more HCC bridging treatments. Median follow-up was 5.3  years. Bridging therapy consisted mainly of transarterial chemotherapy (47.1 per cent), radiofrequency ablation (19.1 per cent), and surgical resection (5.4 per cent) (P = 0.035) and OS  (Table 2). Tumours outside the MC at listing were significantly associated with decreased DFS , but only approached the threshold for significance regarding OS in this cohort.The variables age, time on the waiting list, AFP level before LTx, Milan status at listing (based on imaging), and tumour progression were included in a multivariable Cox regression analysis to determine their influence on DFS and OS in the bridging therapy subgroup. Although time on the waiting list and AFP level before LTx did not significantly affect survival, tumour progression was significantly associated with worse DFS . Mean DFS was 6.5 (95 per cent c.i. 6.1 to 6.9) years in the subgroup inside the MC with controlled tumour growth, compared with 5.5 (4.9 to 6.2) years in the subgroup with tumour progression (P = 0.002) . In the subgroup with disease outside the MC, no difference in DFS was noted between patients with controlled or progressive disease . Similar results were observed for OS. Patients initially inside the MC had significantly better mean OS when bridging resulted in no tumour progression (6.8 (6.4 to 7.1) years; 5-year survival 82.2 per cent) than in those with disease progression (5.8 (5.1 to 6.4) years; 5-year survival 65 per cent) (P < 0.001) . Response to bridging therapy in patients outside the MC did not affect OS; mean survival was 6.2 (5.5 to 7.0) years in patients with controlled disease versus 5.4 (4.6 to 6.2) years in those with progressive disease (P = 0.726) .Tumour progression during bridging and the overall tumour load (MC status at listing) were separated into two subgroups for further survival modelling (versus 6.5 (6.1 to 6.9) years; P = 0.089) and significantly worse OS (5.5 (4.5 to 6.5) versus 6.8 (6.4 to 7.1) years; P = 0.021) than patients whose HCC was controlled during bridging therapy .To analyse whether patients were affected negatively by tumour progression, even if the tumours stayed within the limits of imaging-based MC before LTx, 55 patients on bridging therapy who went from inside to outside the MC were excluded during the waiting period for LTx. In a subsequent analysis including only disease that stayed within the MC, patients with tumour progression during bridging had decreased DFS (mean 5.5 (4.5 to 6.5) Fig. 3). Thirty-seven patients with successful downstaging (out-to-in subgroup) had a mean DFS of 4.7 (95 per cent c.i. 3.7 to 5.6) years and OS of 6.2 (5.0 to 7.3) years, whereas patients who remained within the limits of the MC had superior survival, with mean DFS and OS of 6.3 (5.9 to 6.7) years (P = 0.008) and 6.6 (6.2 to 6.9) years (P = 0.030) respectively. The 5-year survival rate (OS) was 79.5 per cent in patients with HCC never exceeding the MC, compared with 61 per cent among those with disease downstaged from outside the MC.Patients were categorized according to Milan status before and after bridging therapy (at listing (imaging) and at LTx (pathology)). In terms of DFS and OS, 184 patients who remained inside the MC throughout the LTx waiting period had significantly better outcomes than all other subgroups . Some studiesversus outside the MC, controlled versus progressive tumour). It is also worth noting that the study protocol did not require (at that time) a waiting period between bridging and transplantation, as demanded by current UNOS criteria for patients with downstaged HCC.The SiLVER study was neither powered nor initially designed to answer these questions, so limitations should be considered regarding the present analysis. First, bridging modalities were not standardized, and varied in both technique and frequency between study participants. Data acquisition was also limited by the fact that only consistently documented data for imaging at the time of diagnosis and in pathology reports from explanted livers post-LTx were available. Therefore, there was no planned interim analysis of tumour responses during bridging treatment, limiting knowledge about tumour kinetics and responses to therapy before LTx. Furthermore, patient enrolment into the SiLVER study was started in 2006, years before the introduction of the modified RECIST criteria, which would have allowed a more subtle analysis of tumour load and behaviour. This issue was addressed by introducing a simplified, but yet reliable categorization scheme (within Overall, this analysis has highlighted the potential negative prognostic impact of tumour progression in patients with HCC receiving locoregional therapy before LTx. The present results highlight the need for prospective trials that are specifically designed to assess HCC progression under pressure from bridging therapy, before making the critical decision regarding how to best to use organs for LTx.


Rosaceae/Prunoideae fruits and nuts followed by vegetables, Rosacea/Pomoideae fruits, legumes, and cereals. Five out of 38 (13.2%) patients previously sensitized to nsLTP but without allergy to any plant food had experienced allergic reactions to some plant food: two to Rosaceae/Prunoideae fruits, two to Rosaceae/Prunoideae fruit and nuts, and one to legumes. Conclusion: Patients sensitized to nsLTP developed allergic reactions to other plant foods, mainly Rosaceae-Prunoideae fruits and nuts. This was more frequent among plant-food-allergic patients than among those who had never had plant-food allergy.Introduction: Allergy to nonspecific lipid transfer protein (nsLTP) is the main cause of plant-food allergy in Spain. nsLTPs are widely distributed in the plant kingdom and have high cross-reactivity but extremely variable clinical expression. Little is known about the natural evolution of this allergy, which complicates management. The objective of this study was to assess the development of allergy to new plant foods in nsLTP-sensitized patients 10 years after diagnosis. Methods: One hundred fifty-one patients showing specific IgE to nsLTP determined by ISAC (Thermofisher) were included. After clinical workup , these patients were divided into two groups: 113 patients allergic to one or more plant food (74.5%) and 38 patients not allergic to any plant food (25.1%). Ten years later, a telephone interview was conducted to check whether patients had developed additional allergic reactions to plant foods. Results: Ten years after diagnosis, 35 of the 113 (31%) plant-food-allergic patients sensitized to nsLTP reported reactions to new, previously tolerated plant foods, mainly  Food allergy affects around 0.3% to 5.6% of the population, showing substantial geographical variation in prevalence and in terms of the culprit food . AllergyHevea brasiliensis [Nonspecific lipid transfer proteins (nsLTPs) are small, highly stable and conserved molecules involved in the plant defense against fungi and bacteria ,3. nsLTPiliensis . Allergyiliensis ,6,7,8.Fruits of the Rosaceae family are the most frequently involved foods in allergic reactions among nsLTP-allergic patients . AllergyPatients with allergy to nsLTP exhibit considerable clinical heterogeneity, as some react to only one food (often peach), while others may experience symptoms to multiple nsLTPs from allergenic sources that are not taxonomically related and do not follow a defined pattern . The extThe management of patients allergic to nsLTP is complex and poses a major challenge for both allergists and patients. The problem lies in the fact that LTP is a panallergen, meaning that it is a ubiquitous protein that is widely distributed in plant foods and has wide cross-reactivity and a highly variable clinical expression, sometimes eliciting life-threatening reactions. Further complicating this situation is the possibility that patients sensitized to homologous nsLTPs of other plant foods can progress over time from mere sensitization  to severe or even fatal allergic reactions, which has clear implications for the dietary recommendations given to nsLTP-allergic patients.On the other hand, the LEAP study revealed that early food introduction can prevent the onset of allergy , the STOThe management of such patient heterogeneity continues to challenge the expertise of allergists despite the study by Asero et al.  and the The aim of this study was to assess the development of allergy to new plant foods in nsLTP-sensitized patients over 10 years. The results reinforce key points that inform decision-making related to the management of this heterogenous and complex type of allergy.One hundred fifty-one out of 164 patients sensitized to nsLTP as determined by ImmunoCAP™ ISAC  performed during 2009–2011 in the allergy department of Fundación Jiménez Díaz  were included in the study. Thirteen patients (7.9%) were excluded because they did not respond to the follow-up phone call, refused to answer, or did not give consent to participate in the study. After a clinical study (2009–2011) in real-life conditions , patients were divided into 2 groups: 113 patients allergic to plant food (74.8%) and 38 non-food-allergic patients (25.1%). Once a patient was diagnosed with an allergy to a plant food, they were advised to avoid the food in question and continue eating those they tolerated. Ten years later, in 2020–2021, a telephone interview was conducted to determine whether the patients had developed new allergic reactions to previously tolerated plant foods .All patients showed specific IgE to at least one nsLTP  measured by ImmunoCAP™ ISAC following manufacturer recommendations. Results were expressed in ISU (ISAC standardized units).On the one hand, data were collected at the time of diagnosis, including demographic and clinical characteristics of the patients; sensitization to common allergens ; associated rhinitis or asthma; specific IgE to different nsLTPs, profilins, and PR-10 proteins as determined by ImmunoCAP™ ISAC microarray; and data related to plant-food allergy such as the plant food eliciting allergy and symptoms of the reactions, which were categorized into local symptoms, systemic symptoms, and anaphylaxis (two or more organs involved).On the other hand, after the telephone interview, data collected at the time of diagnosis were re-evaluated to distinguish those patients who had developed allergy to nsLTP-related foods during follow-up so as to search for characteristics that could predict progression to allergy in nsLTP syndrome.2 test was used to compare frequencies. Values were considered significant at a p-value of less than 0.05.Statistical analysis was performed with SPSS . Qualitative variables were expressed as percentages and confidence intervals were calculated at 95%. For quantitative variables, means and standard deviation (SD) were calculated, and for specific IgE results, medians and 25th (Q1) and 75th (Q3) percentiles were given. A χOne hundred fifty-one patients sensitized to nsLTP were selected and analyzed for this study. Thirty-eight patients were asymptomatic upon nsLTP-related food exposure and 113 patients were allergic to nsLTP-related plant foods. Characteristics of the patients are shown in One hundred thirteen patients sensitized to nsLTP were allergic to plant food before the start of the follow-up period. Characteristics of the patients are shown in n = 99 out 113 patients tested), with a median positive test value of 3.3 ISU (1.15–5.5 Q1–Q3); 80.6% to Pla a 3 (n = 29/36), median 0.8 ISU (0.6–2.2); 75.9% to Jug r 3 (n = 23/29), median 1 ISU (0.55–1.75); 64.3% to Art v 3 (n = 72/112), median 1.6 ISU (0.6–3.2); 53.1%to Cor a 8 in (n = 59/111), median 1.3 ISU (0.7–3.13); 59.3% to Ara h 9 (n = 16/27), 0.9 ISU (0.5–1.6); and 30.8% to Ole e 7 (n = 8/26), median 1.3 ISU (0.4–2.3). These results are shown in The frequency of sensitization to different nsLTPs (ISAC) at the beginning of the study was as follows: 87.6% to Pru p 3 , Rosacea/Pomoideae fruits (17.4%), lettuce (13.0%), and legumes (8.7%). Sensitization to profilin in this anaphylaxis subgroup was 26% (6 patients) and 30.4% were sensitized to PR-10 (7 patients). The rate of anaphylaxis in profilin-sensitized patients was 7.8%, and 22% of profilin-negative patients presented anaphylaxis.Eighty-five patients (75.2%) developed systemic symptoms, 23 of whom (20%) experienced an anaphylactic reaction. The plant foods responsible for the anaphylactic reactions were as follows: nuts (39.1%), At the start of the study, 38 out of 151 patients sensitized to any nsLTP had not experienced any plant-food allergy. These patients made up the group of non-plant-food-allergic patients. Characteristics of the patients are shown in The most common allergens identified through specific IgE (ISAC) were the following: Pru p 3 in 70.3% (26/37) of patients, median 1.85 ISU (0.8–3.4); Art v 3 in 40.5% (15/37), median value 0.8 ISU (0.6–1.45); Cor a 8 in 37.84% (14/37), 1.05 ISU (0.6–1.4). These results are shown in p = 0.012) and Art v 3 (p = 0.013), but not to Ara h 9, Cor a 8, Jug r 3, Ole e 7, and Pla a 3. Comparisons are shown in There was no statistically significant difference in specific IgE to different nsLTPS between the 2 groups . However, there was a statistically significant difference between the percentage of positive patients between the 2 groups to Pru p 3 (Twenty-five of 156 patients had negative specific IgE to Pru p 3: 14/113 patients (12.4%) from the plant-food-allergy group and 11/38 patients (28.9%) from the group without food allergy.Focusing on the plant-food-allergy group, 5 out of 14 (20%) patients had a systemic reaction, one of which (4%) was an anaphylactic reaction. Despite the negative value for Pru p 3, 9 patients had allergy-related symptoms to peach. Sensitization to nsLTP among Pru p 3-negative patients was as follows: 7 patients (50%) monosensitized to Art v 3, 2 patients to Pla a 3, 1 patient to Cor a 8, and 1 patient to Ara h 9. The other 3 patients were polysensitized with Art v 3 involved in all cases: 1 patient to Cor a 8 and Art v 3, 1 patient to Jug r 3 and Art v 3, and 1 patient to Ara h 9, Jug r 3, Art v 3, and Pla a 3. These results are shown in Nine patients non-sensitized to Pru p 3 were positive for other panallergens: 6 to profilin and 3 to the PR-10 protein family.In the group without food allergy, 5 patients (55.4%) were monosensitized to Art v 3, 3 patients to Cor a 8, and 1 patient to Jug r 3. The other patient was sensitized to both Cor a 8 and Art v 3.Three patients were sensitized to other panallergens: 2 patients to allergens belonging to the PR-10 protein family and 1 patient to profilin.Forty out of 151 patients sensitized to nsLTP  developed symptoms of allergy to new (previously tolerated) plant foods during the follow-up period. Patients in this group had a mean age of 31.4 years (range 2 to 62 years) with a higher prevalence of female patients (60%). In addition, 95% of patients had a history of atopy and 90.2% had current atopy.The frequency of sensitization to different nsLTPs (ISAC) at the beginning of the study was as follows: 85% of 40 patients were sensitized to Pru p 3, with a median value of 2.4 ISU (1.04–4.7 Q1–Q3); 50% of 10 patients to Ara h 9, median 0.9 ISU (0.4–1); 52.5% of 40 patients to Cor a 8, median 1.2 ISU (0.6–0.8); 72.7% of 11 patients to Jug r 3, median 1 ISU (0.9–2.8); 55% of 40 patients to Art v 3, median 1.2 ISU (0.6–2.1); 77% of 13 patients to Pla a 3, mv 1.56 ISU (0.6–2.3); and 11.1% to ole e 7 (one patient). There was no statistical difference in the specific IgE rate to different LTPs between the group of patients that developed allergy to new plant foods or not . In addiRosaceae fruits (13 to Rosaceae/Prunoideae fruits and 3 to Rosaceae/Pomoideae fruits), 16 to nuts (5 patients shared Rosaceae fruits and nuts), 4 patients to vegetables, 2 to cereals, 1 to legumes, and 1 to seeds. The allergy symptoms in these patients were local reactions in 37.1% and systemic reactions in 62.9%; 8.6%  were anaphylactic reactions. All new plant foods that elicited allergic reactions during the follow-up period are shown in Thirty-five  of the 113 patients from the plant-food-allergy group developed allergy to new plant foods: 16 patients to Patients from this group had a mean age of 26.9 years (range 2 to 61 years) and were predominantly female (60%). Sensitization to common allergens was present in 91.43% of the patients; 85.7% of the patients had associated rhinitis while 62.8% presented asthma. Sensitization to profilin was 31.4% and 17.1% were sensitized to PR-10. Nineteen patients received grass pollen immunotherapy and none of them to birch pollen.Rosacea fruits in 2 patients, nuts in 2 patients, and legumes in 1 patient. Two patients from this group developed allergy to both Rosacea fruits and nuts. The allergy symptoms in these patients were local in 60% and systemic in 40%. None experienced anaphylactic reactions.Five out of 38 patients  from the non-food-allergy group, which comprised patients who had never experienced allergic reactions to any plant foods, developed allergy to new plant foods. The plant foods eliciting allergy in this subgroup were as follows: Patients from this group ranged in age from 18 to 50 years (mean age 31.4 years), with a higher prevalence of females (60%). Sensitization to common allergens was present in 100% of the patients. Rhinitis and asthma were also prevalent comorbidities . Profilin sensitization was not found in any patients and 2 patients were sensitized to PR-10 family protein (40%). Three patients received grass pollen immunotherapy and none of them to birch pollen.The present study focuses on the development of allergy to new plant foods among nsLTP-sensitized patients. We consider this unresolved issue to be a key point in the management of nsLTP-allergic patients. Our results reveal that 31% of nsLTP-allergic patients became allergic to new plant foods that had been tolerated at the time of diagnosis. We also found that, after 10 years, 13% of patients simply sensitized to nsLTP developed plant-food allergy.This is a real-life study based on clinical allergy practice. Ten years following diagnosis, a telephone interview was conducted to determine whether patients developed allergies to new plant foods. Real-life studies and the results of the telephone interviews have both advantages and disadvantages which should be considered when interpreting these results. However, we found the results to be valuable as they provide interesting information on the development of allergy to new plant foods, both among patients with nsLTP allergy and among nsLTP-sensitized subjects who have never been allergic to plant foods (latent atopy).To our knowledge, the report by Asero et al.  is the oA literature search revealed no previous studies addressing the development of plant-food allergy among nsLTP-sensitized patients without previous plant-food allergy. We found that allergy to new plant foods among patients without previous plant-food allergy was not only less frequent, but also less severe, as no patients in the sensitized group had anaphylactic reactions. These data support current recommendations indicating that patients who experienced systemic reactions should always carry auto-injectable adrenaline with them.Another finding of our study, and one that is found throughout the literature on nsLTP allergy, is that rosaceous fruits and nuts are the foods most frequently responsible for nsLTP allergic reactions ,19,20, eWe also found that sensitization to profilin and PR-10 allergens appears to decrease the risk of severe reactions ,22, and -Patients should avoid plant foods that provoke allergic reactions after an allergy study based on anamnesis, skin testing, and/or determination of specific IgE and challenge tests when necessary;-Patients with systemic reactions should always carry self-injectable adrenaline on their person;-Additional dietary restrictions should be based on patient risk stratification, as it is impossible to predict severity and/or allergy to new plant foods. In our opinion, key points to stratify the risk of the nsLTP-allergic patients are those appearing in Asero et al.  providedIn summary, one-third of nsLTP-allergic patients developed allergy to novel plant foods, while one-tenth of nsLTP-sensitized patients without food allergy eventually developed reactions to novel plant foods, which were milder. Finally, risk stratification should be a cornerstone of individualized management for highly varied patients with nsLTP allergy.


Endometriosis is an important cause of chronic pain and infertility. Surgery is considered the goldstandard for diagnosis and treatment. In this study, we aim to describe the clinical outcomes of women who undergolaparoscopic surgery for endometriosis.In this cohort study, a total of 174 women who referred to Farmaniyeh Hospital,Tehran, Iran from August 2015 to December 2017 with surgical diagnoses of endometriosis stages III and IVenrolled. The participants’ demographic, gynaecological, and clinical characteristics were recorded and theywere asked to use a numeric rating scale (NRS) to record their severity of pain before and three months aftersurgery. Blood samples were also taken from the patients before and three months after surgery for measurementof serum levels of anti-Müllerian hormone (AMH) and cancer antigen 125 (CA-125). Data were analysed usingSPSS version 21.The patients had a mean age of 34.86 ± 6.47 years, 60.9% were married, and 49.4% were housewives.The primary indication for surgery was pain (68.4%), followed by both pain and infertility in the remainder ofpatients. Types of endometriotic lesions included endometrioma (19%), deep infiltrating endometriosis , and both endometrioma and DIE (77.6%). There was a reduction in pain from 6.79 ± 2.19 before surgeryto 1.48 ± 1.68 after surgery; serum AMH levels reduced from 2.80 ± 1.86 ng/mL to 1.76 ± 1.40 ng/mL and CA-125 reduced from 257.06 ± 220.25 U/mL to 23.27 ± 23.25 U/mL . Of the 21.2% who experiencedrecurrence, 13.5% underwent additional surgery. The total additional surgery rate was 2.8%. Of the 55 patientswith infertility, 78.1% became pregnant after surgery, 54.5% of which was spontaneous.Surgical treatment of endometriosis had a favourable effect on the patients’ pain and inflammation andresolved the patients’ infertility with a minimal need for additional surgery. Endometriosis is a benign gynaecologic disorder mainly observed in reproductive age women that has a globalprevalence of 5-15% ; some caSeveral hypotheses have been proposed for the pathogenesis of endometriosis; however, the majority of patients’ symptoms appear to be associated with inflammation and proliferation of endometriotic lesions  thatresThe clinical symptoms of endometriosis are not specificand serum/peripheral biomarkers can only predict endometriosis ; therefoIn this cohort study, all women who referred to Farmaniyeh Hospital in Tehran, from August 2015 to December 2017 for surgical treatment of endometriosisenrolled in this study. Diagnosis of endometriosis wasbased on the clinical symptoms of endometriosis and theresults of imaging tests (ultrasound and magnetic resonance imaging [MRI]) in patients with severe pain orboth pain and infertility who were indicated for surgical treatment. Those with surgically confirmed endometriosis stages III or IV were included in this studyby the census method, after they received explanationsabout the study objectives and read and sign the writteninformed consent form. The Ethics Committee of Farmaniyeh Hospital approved the study protocol (FH-02-005). This study was conducted in accordance with theprinciples of the Declaration of Helsinki and its subsequent amendments.The surgeries for all enrolled patients were performedby one surgical team of two gynaecologic laparoscopicsurgeon.For this purpose, after induction of general anaesthesia by the anaesthesiologist, the trocars were inserted intheir place and the abdomen and pelvic cavity were explored. After visualization of the endometrioma, the cystwall was excised and the ovarian adhesions were releasedto mobilize the ovaries, and the DIE lesions were totallyresected. The researcher used a study checklist to record theparticipants’ demographic characteristics , gynaecological characteristics , and endometriotic-relatedcharacteristics . The information was collected fromthe hospital medical records and completed by conferring with the patients (history taking). Cases of recurrence, reoperation, and pregnancy after surgery with orwithout assisted reproductive technique (ART) wererecorded. Follow-up information was collected duringpost-surgical follow-up visits or by phone contact withpatients who did not return for their follow-up visits.Recurrence was defined as recurrence of endometriomaor pain. Cases with recurrence were treated by medicaltherapy and surgery, if required.The participants were asked to record their pain severitybefore and three months after surgery on a numeric ratingscale (NRS), which was scored from 0 to 10 where 0 indicated no pain and 10 indicated the worst pain. Two bloodsamples were taken from the patients, one before surgeryand three months after surgery. The samples were sent tothe laboratory for measurement of serum levels of AMHand CA-125 antigen. The tumour markers were measuredusing an Enzyme linked Fluorescent Assay (ELFA) technique (TOSOH Co.) and CA-125 levels <35 were considered normal. AMH was measured using ELISA kits. AMH levels of 4.0-6.8indicated optimal fertility, 2.2-4.0 indicated satisfactoryfertility, 0.3-2.2 indicated low fertility, and <0.3 indicatedvery low fertility.Cases who were not confirmed as having endometriosisby surgical inspection were excluded from the study andnot included in the statistical analysis. The results were described by frequency (%) for categorical variables and by mean ± standard deviation (SD)for quantitative variables. The results of the Kolmogorov-Smirnov test showed normal distribution of the data;therefore, we used the paired t test to compare numericvariables before and after surgery. The chi square testwas used to compare frequencies between the groups. Forstatistical analysis, we used the IBM SPSS Statistics forWindows version 21.0 statistical software. P<0.05 were considered statisticallysignificant. The 174 women who completed the study had amean age of 34.86 ± 6.47 (18-49) years. Most (60.9%)were married, about half (49.4%) were unemployed/housewives, and 64.3% had an academic education. Table1 lists the demographic and gynaecologic characteristicsof the participants. The indication for surgery was painin the majority (68.4%) of patients and both pain andinfertility in the rest.Types of endometriotic lesions included:endometrioma , DIE , and both endometrioma and DIE ; 77.4%of cases with endometrioma were bilateral (n=130)and 22.6% (n=38%) were unilateral. The frequencyof endometrioma located on the left side (57.9%) wassignificantly higher than the right side ,but the frequency of DIE on the left or right sides didnot have any significant difference . As shown, the most common siteof DIE was the ovarian fossa and the least common sitewas the vaginal vault (1.19%).Participants reported a reduction in pain from 6.79 ± 2.19before surgery to 1.48 ± 1.68 after surgery; in addition,serum levels of AMH reduced from 2.80 ± 1.86 ng/mLbefore surgery to 1.76 ± 1.40 ng/mL after surgery and thatof CA-125 from 220.25 ± 257.06 U/mL before surgery to23.27 ± 23.25 U/mL after surgery  and menopause in only seven of our patientsconfirmed the main occurrence of endometriosis inwomen of reproductive age and its rare occurrence aftermenopause . Endometrioma and DIE were present in 96.6% and 81%of patients, respectively, alone or in combination. Thehigh frequency of coexistence of endometrioma and DIErefers to their association, as reported previously .FurtherThe primary endometriosis symptoms in our patientsincluded dysmenorrhea (95.9%) and dyspareunia (58%),while menstruation-related problems such as menorrhagia,metrorrhagia, and irregular menstruation had a frequencyof 20-25%. Different frequencies have been reported inwomen with endometriosis , 17. HowAnother important aspect of endometriosis is infertility.In the present study, the majority of our patients weremarried and infertility was observed in more than halfof the married cases (51.8%) and about one-third ofall cases (31.6%), which referred to the significance ofinfertility in women with endometriosis. The follow-up in our study showed that 78.1% of infertile womenbecame pregnant after surgery, 54.5% were spontaneousand 23.6% after ART. In a study by Alborzi et al. ,58.1% oAs a reliable marker for diagnosis of endometriosis, CA-125 was also measured in the present study and the resultsshowed that the significantly high mean pre-surgical levelof CA-125 reduced after surgery. These results confirmedthe previous study results, considering the high levelof CA-125 in peritoneal fluid and sera of patients withendometriosis  and signThe results of the present study showed that surgicaltreatment of endometriosis could have a favourable effecton patients’ pain and infertility with a minimal rate ofreoperation and acceptable recurrence rate. However, therole of AMH in endometriosis and the serum level of CA-125 after surgery should be studied in future research.


Pediatric primary cardiac tumors (PCTs) are rare. Its clinical features and prognoses are not well defined. The management of asymptomatic patients with cardiac fibromas remains controversial.We aimed to examine our experience in surgical resection of pediatric PCT, with specific focuses on the management of large fibromas.This study included all the children who underwent surgical resection of PCT in our institution between December 2008 and June 2021. The last follow-up was performed between June 1st and August 26th, 2021. Kaplan–Meier method was used to estimate the postoperative survival, freedom from reoperation, event-free survival, and also related risk factors. The tumor volume and volume index (volume divided by body surface area) were measured for cardiac fibromas.Ps > 0.05). The fibroma volume index was negatively correlated with age (P = 0.039), with a mean value of 105 ± 70 ml/m2. Of the 15 patients with fibromas, 5 were asymptomatic, 4 received partial resection, 4 required transmural resection, and 4 presented postoperative left ventricular (LV) dysfunction (ejection fraction <50%). During the median follow-up period of 3.1 years and maximum of 12.5 years, adverse events included 2 early and 1 late death, 4 reoperations, 4 tumor recurrences, and 1 LV dysfunction lasting over one year. The 8-year survival, freedom from reoperation, and event-free survival rates were 90.4, 81.8, and 64.2%, respectively. Malignant tumor (P < 0.001) was associated with more adverse events. Transmural resection (P = 0.022) and larger tumor volume index than LV end-diastolic volume (P = 0.046) were risk factors for LV dysfunction following fibromas resection.Of the 39 patients with median operative age of 9.5 [interquartile range (IQR): 1.2–16.5] years, 35 (89.7%) had benign tumors . The length and volume of fibromas were independent of age and symptoms (Pediatric surgery for PCT can be performed with low mortalities and few adverse events. The size of cardiac fibroma in children relatively decreases with the increase of age. Larger tumor volume index than LV end-diastolic volume index and transmural tumor resection predicts postoperative LV dysfunction. Primary cardiac tumor (PCT) is a rare disease with an incidence of 0.002–0.3% in autopsy series, and approximately 90% of which has benign nature . RhabdomClinical presentations of PCT are variable. The symptoms are associated with intracardiac obstruction, conduction system disturbance, valvular dysfunction, embolization, or systemic symptoms , 3. RhabSurgical tumor resection is safe and effective in eliminating these threats , 10, 14.The inpatient record database of the Second Xiangya Hospital was searched for records of all patients with cardiac mass. Cases that met the following criteria were included: (1) had tissue diagnosis of PCT; (2) underwent surgical resection in our institution; and (3) age at operation ≤ 18 years. Patients with inadequate or unreliable data for diagnosis were excluded. Patients with a tumor of the pericardium were excluded due to the significantly different surgical strategy. A review of medical records was approved by the Institutional Ethics Committee.The study variables are given in Tumors were classified as intramyocardial or intracavitary. Tumor length was the largest dimension of the mass measured by TTE within one month before the operation. The fibroma volume and the patient's LV end-diastolic volume (LVEDV) were retrospectively measured by a radiology professor (Hui Y) based on preoperative MRI or CT angiography (CTA) images. The fibroma volume index was then calculated by dividing the tumor volume by the body surface area. Tumor histotype was rechecked and described according to the 2015 WHO classification of tumors of the heart  classification was measured for subjects ≥10-year-old. Younger subjects were assessed for growth and development status.U-test, unpaired t-test, or Fisher's exact test when appropriate. Correlation coefficients (r) between the fibroma size and patients' age were calculated using Pearson's correlation tests. The Kaplan–Meier method was used to estimate overall survival and event-free survival rate, and freedom from reoperation. The survival curves were truncated when the number at risk is less than 10% of the original cohort. The univariate Cox regression analysis was performed to identify factors associated with time-varying adverse events . Variable with a P-value < 0.20 became a candidate for stepwise backward multivariate Cox regression analysis. Variables were retained when P < 0.10. Results were reported as a coefficient, hazard ratios (HR) with 95% CIs. Similarly, the univariate and multivariate logistic regression analysis was performed to identify factors associated with postoperative LV dysfunction. Results were reported as a coefficient, odds ratios (ORs) with 95% CI. A P-value < 0.05 was considered significant. Data analysis was performed using IBM SPSS Statistics 23.0 .Data were described as mean ± SD, median [interquartile range (IQR)], or frequency (%) when appropriate. Comparisons between the two groups were carried out using a two-tailed Mann–Whitney n = 15) and myxoma (n = 13) were the two commonest benign tumors, followed by rhabdomyoma and lipoma (n = 2 for each), and hamartoma of mature cardiac myocytes, capillary hemangioma, mature teratoma (n = 1 for each). Besides, myxofibrosarcoma (n = 2), rhabdomyosarcoma (n = 1), and papillary angioendothelioma (DabsKa tumor) (n = 1) were identified as malignant tumors  benign and 4 (10.3%) malignant tumors . Fibromat tumors .n = 22) and intracavitary tumors (n = 17) are, respectively, shown in P = 0.003; Detailed characteristics of patients with intramyocardial tumors , followed by interventricular septum (n = 4), right ventricle (n = 2), and left atrium (n = 1). Myxomas were mainly located in the cavitary of the left atrium (n = 5) and right atrium (n = 4). Ventricular myxomas were found in 3 patients . The largest fibroma was shown in Ps > 0.05, P = 0.039. n = 10) and asymptomatic (n = 5) patients . In total, 10 of the 15 (66.7%) patients had a larger fibroma volume index than the LVEDV index.The median length, volume, and volume index of fibromas were 52 mm (IQR: 38 to 56), 59 ml (IQR: 44 to 88), and 101 ml/mn = 2), atrioventricular groove (n = 1), and His bundle (n = 1). Another 4 (26.7%) patients with fibromas received transmural resection resulting in damage to the endocardium. The tumor bed was obliterated using Prolene  suture and reinforced with felt pieces at the outer side  (mean: 116 ± 53 min) and aortic cross-clamping (ACC) (mean: 88 ± 49 min). In total, four of 15 (26.7%) fibromas were partial resected to avoid possible damage to major coronary artery (ter side . One patn = 13) and ACC (n = 9) was 67 ± 32 and 31 ± 28 min for cardiac myxomas resection, both were significantly shorter than that for fibroma resection (Ps < 0.05). Associated procedures were performed in 8 (47.1%) patients, which was more than that in patients with intramyocardial tumors .In general, the diagnosis of an intracavitary cardiac tumor is the indication for its complete resection, especially in patients with symptoms, hemodynamic impairment, or patients with the risk of embolism. In total, six of the 17 (35.3%) patients with right atrial tumor received an operation on beating heart. The mean duration of CPB (There were 2 (5.3%) early deaths. One 5-month-old girl with LV fibroma  sufferedP = 0.014) and underwent transmural resection (P = 0.008) were significantly associated with LV dysfunction in univariate analysis (P = 0.022) and tumor volume index larger than LVEDV index (P = 0.046) are two significant risk factors  patients  presented with LV dysfunction. The duration of CPB  patients. In total, one patient with myxoma and 1 patient with fibroma was lost to follow, respectively, at the 1st and 3rd postoperative years. The median duration of follow-up was 3.1 years with a range from 1 month to 12.5 years.There was 1 (2.6%) late death. This patient presented with left hemiplegia preoperatively and died because of multiple embolisms involving the spleen and renal after 2.8 years. The Kaplan–Meier estimated survival rate was 94.9% at 1 year, and 90.4% both at 5 and 8 years . There wP < 0.001, During the follow-up period, 5 of 6 (83.3%) patients discharged with LV dysfunction recovered within 1 year, another one lasted for 2 years. In total, four (10.3%) patients had recorded tumor recurrence, i.e., 2 myxomas (reoperation respectively at 10 months and 3 years after primary resection), 1 poorly differentiated myxofibrosarcoma ; one patient is in chemotherapy for a recurrence of myxofibrosarcoma; one patient with a history of hemiplegia is in recovering of language function and physical ability; another patient is recovering in hospital after reoperation for LV outflow tract obstruction. The remaining patients are asymptomatic with the NYHA class I/II or with normal growth and development.We presented a comprehensive review of the characteristics of PCT and its prognosis in 39 children. The overall survival and event-free survival rate following surgical tumor resection were 90.4 and 64.2% at 8 years. We highlight the impact of transmural resection and larger tumor size on postoperative course for patients with fibroma.Resection of primary cardiac tumors has been proved as a safe surgical procedure with a low mortality rate. The longitudinal European multicenter study reported early mortality of 4.5% in 89 children . The NatPatients with histologically malignant tumors usually have worse survival outcomes , 14. We 2 was significantly related to postoperative LV dysfunction in the univariate analysis .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. 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Anopheles funestus mosquitoes.The effectiveness of long-lasting insecticidal nets (LLIN), the primary method for preventing malaria in Africa, is compromised by evolution and spread of pyrethroid resistance. Further gains require new insecticides with novel modes of action. Chlorfenapyr is a pyrrole insecticide that disrupts mitochrondrial function and confers no cross-resistance to neurotoxic insecticides. Interceptor® G2 LN (IG2) is an insecticide-mixture LLIN, which combines wash-resistant formulations of chlorfenapyr and the pyrethroid alpha-cypermethrin. The objective was to determine IG2 efficacy under controlled household-like conditions for personal protection and control of wild, pyrethroid-resistant Experimental hut trials tested IG2 efficacy against two positive controls—a chlorfenapyr-treated net and a standard alpha-cypermethrin LLIN, Interceptor LN (IG1)—consistent with World Health Organization (WHO) evaluation guidelines. Mosquito mortality, blood-feeding inhibition, personal protection, repellency and insecticide-induced exiting were recorded after zero and 20 washing cycles. The trial was repeated and analysed using multivariate and meta-analysis.An. funestus mortality was 2.27 (risk ratio 95% CI 1.13–4.56) times greater with unwashed Interceptor G2 than with unwashed Interceptor LN (p = 0.012). There was no significant loss in mortality with IG2 between 0 and 20 washes . Comparison with chlorfenapyr treated net indicated that most mortality was induced by the chlorfenapyr component of IG2 , while comparison with Interceptor LN indicated blood-feeding was inhibited by the pyrethroid component of IG2 . Both insecticide components contributed to exiting from the huts but the contributions were heterogeneous between trials . WHO susceptibility tests with pyrethroid papers recorded 44% survival in An. funestus.In the two trials held in NE Tanzania, An. funestus provides first field evidence of high efficacy against this primary, anthropophilic, malaria vector.The high mortality recorded by IG2 against pyrethroid-resistant  Long-lasting insecticidal nets (LLINs) are essential for malaria transmission control in sub-Saharan Africa . The halAnopheles gambiae complex: An. gambiae sensu stricto (s.s.) in NW Tanzania and Anopheles coluzzii in Benin. However, a third primary vector has re-emerged, Anopheles funestus [An. funestus and An. gambiae was achieved [An. funestus and An. gambiae s.s. is in pyrethroid-resistant form.Pyrethroids, owing to their efficacy, safety and low-cost were once the only insecticides approved for use on LLINs . Since 2funestus , and thiachieved , 21. TheAn. funestus complex has only recently been characterized in Tanzania [An. funestus s.s. (97%) as the predominant species and Anophelesrivulorum (2%) and Anopheles leesoni (1%) as minor sibling species. Plasmodium falciparum CSP positivity was 8.3% for recently collected An. funestus s.s. [Wucheria bancrofti infection rates decreased from 14.8% in the 2005–2007 archived specimens to only 0.5% in newly collected specimens, with 93% of filarial infections confined to An. funestus s.s. The high P. falciparum and decreasing W. bancrofti infections in An. funestus s.s. most likely reflects infection levels of these parasites in the human population and confirms its vectorial importance [An. funestus s.s., 13.6% An. leesoni, 1.5% An. rivulorum, and 0.6% Anopheles parensis [An. funestus s.s., 2% An. rivorulum and 1% An. leesoni [The sibling species, vector competence and insecticide resistance status of the Tanzania . Molecultus s.s. . Wucheriportance . Vector parensis . In Kilo leesoni .Anopheles funestus s.s. and An. gambiae s.s. in addition to being pyrethroid resistant are naturally highly anthropophagic and endophilic. These are the primary vector species to target with the new generation insecticides like chlorfenapyr. Unlike pyrethroids and other conventional public health insecticides which are neurotoxic, chlorfenapyr disrupts the oxidative pathways that enable proton transfer, conversion of ADP to ATP and cellular respiration in mitochondria [chondria , 25. Witchondria , 17. Whechondria , 26.An gambiae complex: An coluzzii, An gambiae s.s. and Anopheles arabiensis [An. funestus s.s. and Anopheles gambiae s.s. IG2 was tested unwashed and after 20 standardized washes as proxy for an ageing net consistent with WHO guidelines for evaluating LLIN. Two other net types served as positive controls: the pyrethroid-only Interceptor LN (IG1) and a net hand-treated with chlorfenapyr SC formulation. While it was anticipated that pyrethroid resistant An. funestus s.s. and An. gambiae s.s. would both be present, on these two occasions only An. funestus s.s. was present in significant densities.Interceptor G2 LN (IG2) is a Dual-AI LLIN developed by the manufacturer BASF SE which is designed to provide protection against pyrethroid-resistant mosquitoes by means of a mixture of chlorfenapyr and alpha-cypermethrin in a long-lasting wash-resistant formulation. The first experimental hut trials of IG2, undertaken in Benin, Burkina Faso and Cote d’Ivoire in West Africa, targeted members of the abiensis , 27, 28.An. gambiae s.s. and An. funestus s.s. are the major malaria vectors [An. funestus collected from Zenet between 2016–2017 results showed all were An. funestus s.s. In World Health Organization insecticide susceptibility tests using permethrin papers conducted on F1 adult mosquitoes from Zeneti in the year before the hut trials, mortality was 56% among An. gambiae s.s. and 62% among An. funestus. In intensity bottle bioassay An. gambiae s.s. showed 30-fold resistance to permethrin relative to susceptible Kisumu strain [Two experimental hut studies were conducted in Muheza district, Tanga region, at the field station in Zeneti , where  vectors , 22. PolThe WHO Phase II evaluation of Interceptor G2 was conducted in 6 experimental huts of the East African design . The ope(i)Untreated polyester net,(ii)Interceptor LN, unwashed(iii)Interceptor LN, washed 20 times(iv)Interceptor G2 LN, unwashed(v)Interceptor G2 LN, washed 20 timesTwo experimental huts trials were undertaken. The first trial was conducted over 54 collection nights between November and December 2015, the second trial was conducted for 36 nights between May and July 2016. The following six treatment arms were included:2.Polyester net, conventionally treated with chlorfenapyr SC formulation  at 200 mg/mWashing of LLINs was done according to WHO Phase II protocols . The intkdr alleles using Taqman PCR [Treatments were rotated between huts each week (3 nets tested 3 times over 9 days or 2 times over a 6-days) with sleepers rotated between huts and treatments each night using a randomized latin square design to adjust for variation in personal attractiveness to mosquitoes or hut positional effect. Each morning mosquitoes were collected and held for 72 h in cups with sugar solution to record any delayed mortality. All dead and surviving mosquitoes were retained on silica gel for molecular identification  and for qman PCR .(i)Deterrence—the proportional reduction of mosquito entry into huts with insecticide treated nets relative to huts with untreated nets(ii)Mortality—the proportion of mosquitoes killed by a treatment relative to the total numbers entering huts with that treatment(iii)killing effect (%) = 100 (Kt-Ku)/Tu, where i) Kt is the number killed in the huts with treated nets, ii) Ku is the number dying in the huts with untreated nets, iii) Tu is the total entering the huts with untreated netsOverall killing effect—the number of mosquitoes killed by a treatment relative to the number dying in the untreated control, as derived from the formula: (iv)Blood-feeding inhibition—the proportional reduction blood-feeding in huts with treated nets relative to the proportion blood-feeding in huts with untreated nets(v)% Personal protection = 100 (Bu-Bt)/Bu, where (i) Bu is the total number of blood-fed mosquitoes in the huts with untreated nets, and (ii) Bt is the total number of blood-fed mosquitoes in huts with treated netsPersonal protection—the reduction in the numbers of mosquitoes blood-feeding in huts with treated nets relative to numbers blood-feeding through untreated nets, as derived from the formula: (vi)Insecticide induced exiting–the proportional increase in exiting from huts with insecticide treated nets relative to the proportion exiting from huts with untreated netsThe outcomes of the hut trials were:2 before presentation.Netting samples were cut from each net before and after washing and after completion of the trial for determination of insecticide content. Determination of alpha-cypermethrin and chlorfenapyr content was performed at BASF  and Walloon Agricultural Research Centre (CRA-W)  using a draft CIPAC method jointly developed by CRA-W and BASF based on CIPAC 454/LN/M/3.1. The method involves extraction of alpha-cypermethrin and chlorfenapyr by ultrasonication at ambient temperature for 30 min in heptane in the presence of dicyclohexyl phthalate as internal standard, by adding citric acid, and determination by gas chromatography with flame ionization detection (GCFID). The insecticide concentration of each sample (g/kg) was converted to mg/mAnopheles gambiae s.s. Kisumu, a laboratory insecticide susceptible strain, originally from Kenya.Anopheles gambiae s.s. Zeneti, a pyrethroid resistant strain of An. gambiae s.s. from Zeneti village containing the L1014S pyrethroid resistance knockdown allele (kdr east) [An. gambiae Kisumu.dr east)  and showAn. gambiae mosquitoes were exposed for 3 min. Mortality was scored at 24 h, 48 h and 72 h post-exposure.These were conducted on standardised washed and unwashed nets to estimate the wash fastness of each net formulation. Five pieces were cut from each net and two replicates of five susceptible or resistant These were conducted on standardised washed and unwashed pieces of Interceptor G2 LN netting after 0 and 20 washes. A total of 100 susceptible and resistant mosquitoes were tested in tunnel tests in replicates of 50 mosquitoes per test in accordance with WHO guidelines . The tunData were entered into an Excel database and transferred to Stata 11  for processing and analysis. Cone bioassays and tunnel test data were analysed using logistic regression for grouped data adjusting for clustering within replicate tests.Proportional outcomes in the experimental hut trial  related to each treatment were assessed using logistic regression for grouped data adjusting for daily collected mosquitoes. In addition to the fixed effect of each treatment, each model included random effects to account for variation between the hut position and sleeper attractiveness. Comparison between numeric outcomes of treatments  was analysed using negative binomial regression with adjustment for variation in the same covariates described above.2 statistic [Risk ratios of mortality, blood-feeding and exiting rates the two trials were pooled using meta-analysis using a random-effects model STATA® statistical analysis software package version 16 . Overall heterogeneity across trials was calculated using Cochrane’s Q test with a P value of less than 0.05 to indicate statistical heterogeneity and quantified heterogeneity using the Itatistic , 36.An. gambiae and 56.7% for An. funestus in the first trial (2015) and 43% and 52.6%, respectively in the second (2016), indicating resistance to pyrethroids in both species. Mortality using 0.05% alpha-cypermethrin papers was 52.7% for An. gambiae during the first trial. Alpha-cypermethrin papers were not available during the 2nd trial, but other alpha-cyano pyrethroids such as 0.05% deltamethrin and 0.05% lambdacyhalothrin gave a similar 73.8% and 50.6% mortality respectively. Concurrent mortality using the same insecticide test papers against susceptible An. gambiae Kisumu was 100% in each case. Insecticide resistance intensity testing showed Zenet field An. gambiae to have over 30-fold resistance to pyrethroid (permethrin) compared to susceptible An. gambiae Kisumu.WHO susceptibility tests using permethrin and alpha-cypermethrin treated papers were conducted against F1 progeny of mosquitoes collected from huts containing untreated nets before and during the trial. Mortality recorded using 0.75% permethrin papers was 46.7% for An. funestus collected during the first trial ranged from 0.6 to 1.5 per hut per night. During the second trial the geometric mean number of An. funestus ranged from 1.3 to 1.8 per hut per night. In both trials significantly fewer An. funestus were collected from the huts with chlorfenapyr CTN compared to the huts with the untreated nets. No consistent deterrent effect was observed with IG1  or IG2 compared to untreated nets.The average number of mosquitoes entering and exiting the hut are shown in Table The overall percentage mortality by treatment arm is shown in Fig. An. funestus after 24 h was 5–6% in the huts with the unwashed IG1 and in the huts with the IG1 washed 20 times , the IG2 washed 20 times (from 6 to 41%) and the chlorfenapyr CTN (from 18 to 36%)  than the overall mortality in huts with the IG1 unwashed (37%) or IG1 washed 20 times (34%). In the second trial, natural mortality after 72 h in huts with the untreated nets was lower (13%) than in the first trial (21%), but on this occasion the untreated nets showed no difference in mortality compared to IG1 unwashed (16%) or IG1 washed 20 times (18%) which also stayed low. A further difference between the two trials: in the first, both IG2 and IG1 showed significantly delayed mortality between 24 and 72 h, in the second trial only IG2 showed significantly delayed mortality between 24 and 72 h and not IG1.Natural mortality of Because the untreated net control showed 21%  and 13%  mortality after the 72 h holding period, the observed mortality of IG2 presented in Fig. An. funestus, respectively, and IG2 killed up to 49% and 38%, respectively.The ‘overall killing effect’ by the IG1 and IG2 interventions were consistent with percentage mortality of the IG1 and IG2 treatments observed in the huts. In the first and second trials, IG1 killed up to 16% and 0% of In the meta-analyses of mortality between the two trials, the comparison of relative risk between the unwashed IG2 and the untreated net was 3.36  (P = 0.001). The comparison of mortality relative risk between the chlorfenapyr CTN and untreated net, 3.24  (P = 0.001) was, therefore, quite similar to that of the unwashed IG2 and untreated net. The comparison of relative risk between the unwashed IG1 and the untreated net was rather less  (P = 0.01), indicating a smaller effect size of alpha-cypermethrin on mortality. The effect of the comparison between IG2 and IG1 was 2.27  (P = 0.012), confirming the greater contribution of chlorfenapyr than of alphacypermethrin to IG2 mortality. This was further confirmed by the comparison of chlorfenapyr CTN to IG2: the risk ratio was a non-significant 0.96  (P = 0.231) implying that chlorfenapyr was making most of the contribution to mortality in IG2 and not alpha-cypermethrin. The similarity of relative risk between unwashed IG2 and IG2 after 20 washes  (P = 0.73) indicated no loss of mortality effect in IG2 between 0 and 20 washes  (P = 0.133). The comparison of relative risk between the unwashed IG1 versus the untreated net was also quite similar  (P = 0.035) to that of IG2 above  was significantly different from unity  compared to IG1 (4/11) or untreated nets (1/10) (Supplementary file), which is consistent with the An. funestus dataset trends. Insufficient An. gambiae were collected during trial 2 for formal analysis.Abundance of The mean alpha-cypermethrin content in unwashed IG2 for trial 2  was 2.81 g/kg Table . The netAn gambiae s.s.The purpose of the supplementary bioassays was to sample netting from the IG2 and IG1 used in the experimental hut trials to 1) test bio-efficacy against pyrethroid resistant (Zenet) and susceptible (Kisumu) strains in mosquito bioassay, 2) confirm the bioefficacy of alpha-cypermethrin and chlorfenapyr components after multiple washing, 3) examine the capacity of tunnel tests to predict the performance IG2 netting under simulated hut conditions to control Standard WHO Cone bioassay tests on nets with 3 min exposure of the susceptible strain and a 72 h holding period, induced mortality of 96% and 100% on the unwashed IG1 and the IG1 washed 20 times. With the chlorfenapyr CTN, mortality was 90%, 95% and 100% after 24 h, 48 h and 72 h. For the unwashed IG2, mortality was 100% after 24 h exposure. For IG2 washed 20 times mortality was 62%, 72% and 86% after 24 h, 48 h and 72 h intervals . When tested against the unwashed IG2, mortality was 40% in the cone, 36% in the tunnel and 51% in the hut; when tested with the 20 times washed IG2 mortality was 20% in the cone, 26% in the tunnel and 46% in the hut.Comparing the laboratory cone and tunnel bioassay results against the pyrethroid resistant With the unwashed and washed IG2, percentage passage and percentage blood-feeding in the tunnel test were significantly lower with the newly-colonised resistant Zenet strain as compared to the long-established susceptible Kisumu strain. While up to 70% of Kisumu blood-fed after penetrating the IG2 netting, none (0%) of the Zenet strain blood-fed through IG2. And while high mortality of Kisumu (up to 70%) was recorded with IG2, low mortality was recorded against unwashed and washed IG2 . This very much reflected the new adaptation of the Zenet strain to the tunnel test, possibly an avoidance or irritation of the treated net, or ‘reluctance’ to feed on guinea pigs. However, for those Zenet strain mosquitoes that did penetrate the netting, mortality inflicted by unwashed and 20 times washed IG2 was high, 58% and 80% respectively, and more closely resembled mortality in experimental huts.An. gambiae and An. funestus. The tunnel tests were more predictive of efficacy in experimental huts whilst cone bioassays were less predictive.This series of bioassay tests demonstrates that the chlorfenapyr component of IG2 LN makes the major contribution to controlling pyrethroid resistant An. funestus and An. gambiae s.s. under household-like conditions compared to the standard pyrethroid-only net Interceptor LN (IG1). Previously this very team had participated in the development and evaluation of IG1 against An. funestus and An. gambiae s.s. 10–14 years ago when these species were pyrethroid susceptible in NE Tanzania [An. gambiae sibling species An. coluzzii in Benin, W Africa, and An. arabiensis in Kilimananjaro, Tanzania, where the species had become pyrethroid resistant [An. gambiae s.s. and An. funestus. Only An. funestus was caught in significant numbers. In the meta-analysis of the two trials, the mortality induced by IG2 against An. funestus was 3.4 times higher than with untreated nets and 2.3 times higher than with IG1. The comparison of mosquito mortality between the unwashed IG2 and IG2 washed 20 times produced a relative risk of 1.04 (CI 0.83–1.30) indicating no loss of efficacy of IG2 over 20 washes. This means IG2 exceeds by a factor of 2.3 the mortality criterion required by WHO PQT to grant the product LLIN status [An. funestus in IG1 and 30% protection in IG2 compared to untreated nets. This was not far short of the 32% blood-feeding inhibition shown by IG1 against pyrethroid-susceptible An. funestus in Zenet hut trials over 10 years ago [Novel alternative insecticides which can complement the pyrethroids on LLIN and improve the control of pyrethroid resistant vectors are urgently needed to sustain progress against malaria. The objective of the present study was to determine the efficacy and wash-fastness of the chlorfenapyr-alphacypermethrin mixture net, Interceptor G2 LN, unwashed and after 20 washes, against the primary pyrethroid-resistant vectors Tanzania , 20. Latesistant –17. Two N status . The comAn. funestus was the clear demonstration of superior mortality of IG2 against resistant An. funestus that approached the mortality that IG1 once showed against An. funestus and An. gambiae s.s. in NE Tanzania before resistance evolved. In 2010, IG1 induced a control-corrected mortality of 80% among susceptible An. funestus when unwashed and 60% after 20 washes. In 2015–2016, IG1 only induced a control-corrected mortality of 12% among pyrethroid resistant An. funestus unwashed and of 11% after 20 washes. In contrast, IG2 induced a control-corrected mean mortality of 49% among pyrethroid resistant An. funestus when unwashed and 52% after 20 washes. While the performance of unwashed IG2 did fall a little short of the mortality induced by unwashed IG1 in 2006 against susceptible An. funestus, the mortality that the 20-times washed IG2 demonstrated against resistant An. funestus in 2016 was comparable to the efficacy 20-times washed IG1 demonstrated against susceptible An. funestus in 2006. Other recent experimental hut trials in West Africa in which IG2 has generated high mortality include An. coluzzii in Benin , in Burkina Faso  and Côte d’Ivoire  when unwashed and washed 20 times, respectively. This is comparable mortality to that achieved with IG1 and other pyrethroid-only nets in the 1990s and new millennium when standard ITN and LLIN were first demonstrating malaria control and personal protection [More important than the demonstration of equivalence of blood-feeding inhibition in resistant otection . ConsideIt is certainly the case that high intensity resistance means that standard LLIN are no longer preventing malaria as they once did. In countries and regions bordering Lake Victoria, for example, standard LLIN no longer appear to be reducing malaria despite maintenance of high coverage , 38, 39.The only putative insecticide mixture LLIN on the horizon, apart from the pyrethroid-chlorfenapyr net IG2, is a net treated with pyrethroid and pyriproxifen which is a mosquito sterilant and insect growth regulator. In a stepped wedge cluster randomised trial conducted in Burkina Faso a reduced malaria incidence rate of 12% was observed in the intervention arm compared to the control, a standard pyrethroid-only LLIN , 41. As An. funestus induced by unwashed and 20 times washed Interceptor G2 appears to meet the entomological requirements set by the WHO for efficacy and wash-resistance. Thus far there is no epidemiological evidence to back up the entomological evidence nor any knowledge of how long Interceptor G2 LN or its chlorfenapyr component will remain effective under field conditions. Therefore, large-scale cluster randomized trials of Interceptor G2 with epidemiological end-points are an essential next step. A CRT in NW Tanzania against An. funestus and An. gambiae is due to report in mid-2021 for recommendation as a new class of LLIN product to WHO.Novel alternative insecticides suitable that can complement the pyrethroids and improve the control of pyrethroid resistant malaria vectors are urgently required for sustaining LLIN as a means of malaria control. The mortality of pyrethroid resistant


Monitoring the population‐level emergence and transmission of HIV drug resistance (HIVDR) is necessary for supporting public health programmes. This study provides a nationally representative prevalence estimate of HIVDR in people initiating antiretroviral therapy (ART) and estimates of acquired HIVDR and viral load (VL) suppression in people who have received it for 12 or ≥48 months in Vietnam.The study was conducted between September 2017 and March 2018 following World Health Organization guidance. Thirty ART clinics were randomly sampled using probability proportional to size sampling from a total of 367 ART clinics in the country.In total, 409 patients initiating ART were enrolled into the survey of pre‐treatment HIVDR. The prevalence of any pre‐treatment HIVDR was 5.8% (95% CI 3.4–9.5%), and the prevalence of non‐nucleoside reverse transcriptase inhibitor resistance was 3.4% (95% CI 1.8–6.2%). Four hundred twenty‐nine patients on ART for 12±3 months and 723 patients on ART for ≥48 months were enrolled into the surveys of acquired HIVDR. The prevalence of VL suppression (defined as <1000 copies/ml) in patients on ART for 12±3 and ≥48 months was 95.5% (95% CI 91.3–97.8%) and 96.1% (95% CI 93.2–97.8%), respectively. Among individuals with viral non‐suppression, any HIVDR was detected in 11/14  of those on ART for 12±3 months and in 24/27  of those receiving ART for ≥48 months.This nationally representative study of HIVDR found high levels of VL suppression among those on ART for 12 and ≥48 months. Overall, high levels of VL suppression at both time points suggested good adherence among patients receiving ART and quality of treatment services in Vietnam.Not applicable As of December 2020, there was an estimated 215,000 people living with HIV in Vietnam and about 70% of them were receiving ART . The preIn 2019, WHO reported HIV drug resistance (HIVDR) data from 44 nationally representative HIVDR surveys from 24 low‐ and middle‐income countries, including Vietnam. In this work, we report prevalence estimates of pre‐treatment HIV drug resistance (PDR) among people starting ART and the prevalence of VL suppression and ADR among those taking ART.22.1We conducted a nationally representative cross‐sectional study of PDR and ADR in adults receiving ART for 12±3 months (ADR12) and ≥48 months (ADR48+). At the end of 2016, Vietnam had a total of 367 ART outpatient clinics (OPCs) providing ART to 105,938 adults. Of the 263 OPCs in operation for ≥48 months , 25 were sampled to contribute to the PDR, ADR12 and ADR48+ month surveys. Of the remaining 104 OPCs in operation for <48 months, five OPCs were sampled to contribute to the PDR and ADR12 months study. This sampling approach maximized overlap in sites contributing to each of the three time points [2.2The PDR survey included people living with HIV (PLHV) presenting to sampled clinics for ART initiation for the first time or re‐initiation of ART if they were on it for less than 1 month and had stopped it for more than 3 months. For ADR surveys, PLHV who have been receiving ART for 12 (±3) months (ADR12) or for ≥48 months were enrolled. All participants in PDR and ADR surveys were 18 years of age or older and provided written informed consent.2.3Sample size calculation followed procedures described by WHO for two‐stage cluster sampling for combined PDR and ADR surveys , 5. The 2.4All participating OPCs consecutively enrolled eligible patients until reaching the target site‐specific sample size or passing 6 months of the study start date, whichever came first.Whole blood specimens were collected for plasma VL measurement in both PDR and ADR survey populations. Collecting and processing of specimens followed WHO laboratory guidance . Specime2.5Data were double entered using Epi Data 3.0  and statistical analysis was performed using STATA version 14  following WHO methods. The prevalence of VL suppression and HIVDR were estimated using STATA's survey (SVY) commands . Data we2.6The study was reviewed and approved by the Institutional Review Board in Biomedical Research, National Institute of Hygiene and Epidemiology, Hanoi, Vietnam .3Thirty randomly sampled OPCs enrolled patients from September 2017 to March 2018 across 18 of 63 provinces in Vietnam. During the 6 months of the study, the number of eligible patients presenting to OPCs were 1150 across 30 OPCs in the PDR group, 1829 across 30 OPCs in the ADR12 group and 12,199 across 25 OPCs in the ADR48+ group. A total of 1561 patients were enrolled in the survey: 409 patients in the PDR survey, 429 patients in the ADR12 survey and 723 patients in the ADR48+ survey.Among the 409 people enrolled in the PDR survey, VL was detectable in 393 (96.1%) with 375/409 (91.7%) having VLs >1000 copies/ml. The genotyping success rate was 340/375 (90.7%). A total of 340 genotypes are available from the PDR survey. HIV‐1 subtype CRF01_AE was the predominant subtype and identified in 328/340 (97.1%) patients. Other subtypes included: subtypes B , subtype C  and CRF07_BC and CRF25_cp (each of 1% or 0.1%).In the ADR survey, genotyping was performed only for patients with non‐suppressed VLs (VL >1000 copies/ml). Viral non‐suppression was documented in 18/429 patients (4.2%) receiving ART for 12 months and 32/723 patients (4.4%) receiving ≥48 months.3.1p = 0.013).We enrolled 409 patients who presented to OPC for ARV drugs. Participant characteristics are summarized in Table Estimates of PDR are summarized in Table p = 0.02).In specimens with any HIVDR, non‐nucleoside reverse transcriptase inhibitor (NNRTI) resistance was predicted in 15/22 (68.2%); one had NVP resistance, and 14 had NVP and EFV resistance. NRTI resistance was predicted in 13/22 (59.1%), and 6/22 (27.3%) had resistance to both NNRTI and NRTI. The nationally representative prevalence of PDR to the NNRTI drug class was 3.4% (95% CI 1.8–6.2%)  patients with successful genotyping, 11 had any HIVDR . The prevalence of any HIVDR among those on ART12±3 months was 3.0% (95% CI 1.6–5.7%). All 11 patients with any HIVDR had NNRTI resistance and nine had NRTI resistance. No PI resistance was observed.3.3A total of 723 patients from 25 clinics were included in the ADR48+ survey Table .The VL suppression and ADR outcomes are summarized in Table p = 0.39 by Fisher's exact test)  was similar to that observed in people receiving ART for at least 48 months (3.4%) , which was seen in 2014 among people on ART for at least 36 months (4.6%) .Vietnam has initiated the transition to dolutegravir containing regimens as preferred first‐ and second‐line regimens since 2020 . A thirdOur report has limitations. Firstly, our results were not reported in a timely manner. However, the data were included in the global report and Vietnam has considered these results and decided to continue the first‐line ART regimen containing NNRTIs and keep improving the quality of ART service. Secondly, we were not able to evaluate the HIVDR when the VL was less than 1000 copies/ml. However, we assumed that the prevalence of HIVDR among patient with suppressed VL was low and this issue is recognized as a technical limitation in other studies .4Vietnam achieved very high level of HIV VL suppression among people on ART and maintained moderate prevalence of HIVDR in patients starting ART and low prevalence of HIVDR in patients receiving ART.The authors declare that there are no competing interests.QD, ND, MRJ, SB and VN developed study protocol, analysed data, interpreted the results and wrote the manuscript. NA, KN, NL, HT, MT, TT, QA, NP, PH, DN and NH contributed to protocol development, monitoring survey implementation and reviewed the manuscript. NA, NL, HT, TT and LQA were involved in the protocol development, performed viral load testing and genotyping and reviewed the manuscript. QD, AC, ND, MRJ and SI performed data analysis. All authors revised the manuscript and approved the final draft.This work is supported by the Global Fund to Fight AIDS, Tuberculosis and Malaria and the World Health Organization.The views expressed in this paper are those of the authors and do not necessarily represent the official position of the authors’ institutions and World Health Organization.


Malignant pleural mesothelioma is an infrequent neoplasia with a poor prognosis and the majority of patients already have advanced disease at the time of presentation. Exposure to asbestos is the most important risk factor for malignant pleural mesothelioma. Mesothelioma is a neoplasia with a long preclinical stage that can span from 15 to 40 years.This was a descriptive, observational, retrospective study of 136 patients with a confirmed diagnosis of mesothelioma, which compared histological subtypes, immunohistochemical biomarkers, concomitant chronic degenerative diseases, tobacco use, age at the time of diagnosis, clinical stage and chemotherapy agents used or other treatments such as radiotherapy and surgery to identify all the factors that impact in the prognosis of overall survival (OS) and progression‐free survival (PFS).A total of 136 patients were included in the study. In the total study population, 84 patients were male (61.8%) and 52 were female (38.2%). Median PFS was nine months  and median OS was 12 months (95% CI: 11.3–12.6). The results indicated that the most determining prognostic factors for OS and PFS were cell differentiation measured by immunohistochemical biomarkers, the treatment chosen, and that RECIST was the most significant in the evaluation of patient response to treatment.Malignant pleural mesothelioma is a cancer with a poor prognosis usually diagnosed at an advanced stage of disease. Our study revealed that the prognostic factors for OS and PS were cell differentiation, the treatment chosen and RECIST. Malignant pleural mesothelioma is an infrequent neoplasm with a poor prognosis and the majority of patients already have advanced disease at the time of diagnosis. In the United States, between two and three thousand new cases are diagnosed every year.In Mexico, the global dimension of this condition is only partially known as clinical reports are scarce and it is estimated that around 70% of cases are underreported. The approximate number of deaths every year due to mesothelioma is 250 but that figure is probably much higher taking into account the cases which are not reported.Exposure to asbestos is the most important risk factor for malignant pleural mesothelioma. Mexico has multiple asbestos deposits that represent a risk to people who live near to those deposits.The majority of reported series in the literature mention that a history of exposure to asbestos is present in 60%–80% of cases of malignant mesothelioma. In the United States it is estimated that 21 million people working in the construction industry are at risk of asbestos exposure; however, the relatively low incidence of this malignancy makes it essential to search for other etiologies that could predispose the appearance of this neoplasm.The length of time of exposure to asbestos is important because longer periods of exposure increase the burden to the lungs, offsetting the effects of solubility of the fibers and with that it can induce or produce diverse respiratory diseases such as asbestosis, mesothelioma and lung cancer. Mesothelioma is a neoplasia with a long preclinical stage that can span from 15 to 40 years. It has a higher prevalence in males with a male to female ratio of five, and the risk increases with age with a range in diagnosis of 45 to 82 years of age and a median of 72 years.Malignant pleural mesothelioma is a disease that requires a multidisciplinary approach where different specialties such as Surgery, Medical Oncology, Pulmonary Medicine, Radiotherapy and Pulmonary Rehabilitation among others converge to design a plan for each patient. However, even with this approach, the median overall survival (OS) has been reported to range between nine and 17 months.After initial evaluation, approximately 80% of patients diagnosed with pleural mesothelioma will not be considered candidates for a multidisciplinary approach that includes definitive surgery.In terms of comparing extrapleural pneumonectomy with pleurotomy/decortication there are no randomized, controlled studies which contrast these two surgical techniques, in the same way there are no controlled studies comparing surgery versus nonsurgical treatment. The current studies are retrospective in nature, have different types of patient cohorts and lack a control group .There are several reasons why the surgical treatment of mesothelioma is challenging: (i) Dissemination through the pleural serous surface with early infiltration of the subjacent structures makes a complete surgical resection very challengingRadiotherapy on its own is not as effective as primary treatment due to the multifocal nature of the malignancy requiring wide fields of radiation. It is also very difficult to achieve sufficient doses of radiation to accomplish adequate control. Moreover, the required doses are intolerable to the lungs and probably also carry a high cardiac toxicity. The results of chemotherapy in terms of partial response are in the region of 15% to 20%. Complete responses are rare. As a stand‐alone treatment, radiotherapy and chemotherapy have a very limited role in the treatment of mesothelioma, and the best treatment strategy is a combination of these two modalities with surgery.A multidisciplinary approach to treatment is based on the evaluation of the extension of the disease, the overall functional status of the patient including his or her cardiopulmonary status, recognition of other comorbidities and the desire or not to pursue an aggressive treatment. We therefore divided patients into two categories.Surgical candidates: Defined as those who have a surgically resectable disease limited to one hemithorax and have no medical contraindications for surgery. In these patients, a combined modality conducive to a possible cure is embraced, incorporating surgery directed to a complete resection along with chemotherapy and radiotherapy.Nonsurgical candidates: These are patients where a complete surgical resection is not possible and those who due to other medical conditions such as advanced age, inadequate cardiopulmonary reserve or significant comorbidities cannot undergo a major surgical procedure. In these patients, systemic palliative chemotherapy and treatment directed to control their symptoms are of most benefit and have a positive impact on their quality of life.Combined chemotherapy using a regimen of cisplatin plus pemetrexed became the most utilized regimen based on a Phase III study that showed an increase in OS compared to cisplatin therapy alone. Ever since, this has been the standard of therapy in our institution, although the French MAPS study reports data supporting the addition of bevacizumab to this regimen.8In the EMPHACIS trial, 456 patients were treated with cisplatin at standard doses and then randomized to receive either pemetrexed or a placebo every three weeks. The median survival rate was statistically better with the combination (12.1 vs. 9.3 months) as well as the time to progression of the disease (5.7 vs. 3.9 months) and the rate of an objective response (41% vs. 17%). The EMPHACIS trial did not have an arm to assess the effects of maintenance with pemetrexed.9,10The results of the MAPS study have established the combination of cisplatin‐pemetrexed‐bevacizumab as the accepted standard of therapy in France for patients with mesothelioma. The National Comprehensive Cancer Network (NCCN) guidelines have included this regimen as an option to the standard first line therapy. In this study, after a median 39 months follow‐up, the progression‐free survival (PFS) increased significantly with the addition of bevacizumab in comparison with the combination of cisplatin and pemetrexed . Furthermore, the overall global survival increased significantly with the triple therapy .There are several ways to evaluate the clinical benefit of treatment: Rate of response, rate of control of the disease, PFS and OS.The rate of objective response and PFS have been utilized as parameters of the efficacy of treatment in previous studies. In the studies on malignant pleural mesothelioma there are two systems of radiographic measurement employed through chest computed tomography (CT) scan, Response Evaluation Criteria in Solid Tumors (RECIST) and Modified RECIST. Modified RECIST measures the pleural cortex or the mass thickness perpendicular to the chest wall in two positions and three separate levels in a chest CT. The sum of these six measurements is used to define the response utilizing the RECIST criteria which is one of the variables used in our study to evaluate the response to treatment.One of the most recent series addressing the prognostic factors in mesothelioma was carried out in Taiwan. This series postulated the following variables as significant prognostic factors in patients with advanced pleural mesothelioma: Age, clinical stage, histological subtype and functional status of the patient. Surgical treatment was independently associated with a favorable prognosis in potentially resectable disease , whereas systemic chemotherapy was an independent predictor of longer OS in patients with advanced malignant pleural mesothelioma (stage III and IV). This was one of the largest series of cases with this pathology in Asia, outside of Japan. The details of every patient in this study allowed for an integral adjustment of prognostic factors together with other previous studies based in registries of Asian countries.The male prevalence reached up to 90% of the patients, and the epithelioid histological subtype was present in more than half of the patients with mesothelioma in this retrospective analysis. The frequency of sarcomatoid and biphasic subtypes was reported to be between 10% and 20%.In the Mexican population there have been only a small number of studies to determine prognostic factors. In one of these, molecular markers such as BCL‐2, p27, MIB‐1 and p53 antibodies, were obtained. The rate of positivity was 2% for the BCL‐2, 61.2% for the p27, 70.5% for the MIB‐1 and 42.1% for the p53. The survival period also showed statistical significance with an increase in the molecular markers and tumor cellular proliferation with the advancement of the disease. A Cox survival analysis did not show a statistical significance when comparing some clinical variables recognized as risk factors. This study suggested that the expression of p27, p53 and MIB‐1 is associated with prognosis in patients with malignant pleural mesothelioma.This was a descriptive, observational, retrospective study of 136 patients with a confirmed diagnosis of mesothelioma, comparing histological subtypes, immunohistochemical biomarkers, concomitant chronic degenerative diseases, tobacco use, age at the time of diagnosis, clinical stage and chemotherapy agents used or other treatments such as radiotherapy and surgery to identify all the factors that impact the prognosis, OS and PFS. The study design was approved by the Instituto Nacional de Enfermedades Respiratorias Institutional Ethics Board following the Declaration of Helsinki, Fortaleza Brazil, 2013. The study population met the following criteria: Patients of 18 years of age or older with a confirmed histopathological diagnosis of mesothelioma, and ECOG 0–3, locally advanced and/or metastatic clinical stage. The following clinical and pathological variables were reviewed: Sex, age, smoking status, asbestos exposure, diagnosis, immunohistochemical biomarkers, treatment used, Eastern Cooperative Oncology Group (ECOG) 0–3, TNM initial clinical stage, response to treatment, PFS and response as per Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1) using computed tomography (CT) scan.P < 0.05. All financially related issues from the study were absorbed by the investigation group.SPSS software version 24.0  was used for analysis. The variables were expressed as median values, together with total values and percentages. PFS and OS were graphed using a Kaplan‐Meier plot. The criterion for statistical significance was A total of 136 patients were included in the study. From the total study population, 84 patients were male (61.8%) and 52 were female (38.2%). The average age was 68 years with a range of 41 to 90 years. Median weight at the time of diagnosis was 59.4 kg (range: 43–90 kg). A total of 92 patients (67.7%) had a confirmed history of tobacco use (current or former smoker), 37 (27.2%) had a confirmed history of diabetes mellitus and 62 (45.6%) of systemic arterial hypertension. One patient (0.7%) had an ECOG score of 0, 34 patients (25.0%) an ECOG score of 1, 91 (66.9%) an ECOG score of 2 and 10 patients (7.4%) an ECOG score of 3. Of all 136 patients, 84 (61.8%) were at clinical stage IV, 26 (19.1%) were at clinical stage III, 14 (10.3%) were at clinical stage II and 12 .A total of 136 patients with a diagnosis of mesothelioma were studied, of which 130 (95.6%) had epithelioid histological type, three (2.2%) had sarcomatoid type and three (2.2%) had a biphasic type. Of those histological types, 100 (73.5%) patients had solid subtype, 12 (8.8%) had tubulopapillary, six (4.4%) had acinar subtype, six (4.4%) patients had micropapillary subtype, five (3.7%) had solid papillary subtype, one (0.7%) had tubuloacinar subtype, one (0.7%) had papillary subtype and one (0.7%) had pleomorphic subtype. A total of 93 (68.4%) patients were examined for nuclear calretinin of which 54 (39.7%) were positive (+++), 23 (16.9%) ++, 14 (10.3%) + and two (1.5%) were negative. A total of 92 (67.6%) patients were examined for cytoplasmic calretinin of which 54 (39.7%) were positive (+++), 25 (18.4%) ++, 11 (8.1%) + and two (1.5%) were negative. For nuclear WT1 95 (69.9%) patients were evaluated. A total of 57 (41.9%) were positive +++, 25 (18.4%) were ++, 11 (8.1%) were + and two (1.5%) were negative. Cytoplasmic WT1 was evaluated in three (2.2%) patients and only one (0.7%) was positive (+++). A total of 72 patients (52.9%) were studied for CK‐5/6 and 28 (20.6%) were positive +++, 17 (12.5%) were ++, 17 (12.5%) were + and 10 (7.4%) were negative. CK‐7 was evaluated in 68 patients (50.0%) of which 35 (25.7%) were positive +++, 23 (16.9%) were ++, four (2.9%) were + and six (4.4.%) were negative. As for cytoplasmic HBM1, 65 patients (47.8%) were examined. A total of 35 (25.7%) had +++, 22 (16.2%) had ++, seven (5.1%) had + and one (0.7%) was negative. For BerEp4 15 patients were evaluated (11.0%) of which six (4.4.%) were positive (+++), five (3.7%) were ++ and four (2.9%) were negative. For EMA, 38 patients were studied (27.9%). A total of 23 (16.9%) were positive +++, nine (6.6%) were positive ++, three (2.2%) were positive + and three (2.2%) were negative. A total of 88 (64.7%) patients were evaluated for TTF1 and none were positive. A total of 18 patients (13.2%) were examined for CD‐99, and 11 (8.1%) were positive +++, six (4.4%) were ++ and one (0.7%) was +. For CK20, 15 (11.0%) patients were evaluated, eight (5.9%) were positive +++, six (4.4%) were ++ and one (0.7%) was +. A total of 83 patients (61.0%) were studied for Reβ and 58 (42.6%) were positive +++, 12 (8.8%) were ++ and 13 (9.6%) were +.Site of metastasis was evaluated and in 109 (80.1%) patients there was no evidence of metastasis, five (3.7%) had metastasis in the lungs, one (0.7%) had metastasis in the central nervous system, four (2.9%) had malignant pleural effusion, seven (5.1%) had metastases in the adrenal glands and 10 (7.4%) had metastases at other sites.Of all 136 patients, 81 (59.6%) received pemetrexed/carboplatin, 24 (17.6%) patients received gemcitabine/carboplatin, 12 (8.8%) received pemetrexed/cisplatin, 11 (8.1%) received gemcitabine, seven (5.1%) received gemcitabine/cisplatin and one (0.7%) received vinorelbine/cisplatin. The median of cycles received was six (1–13). After evaluating the response to chemotherapy by RECIST 1.1, we found 25 patients (18.4%) with a partial response, 84 (61.8%) with stable disease, 10 (7.4%) with complete response and 17 (12.5%) with progression. In addition, 18 patients (13.2%) received radiotherapy, 19 (14.0%) had surgery of which nine (6.6%) had pleuropneumonectomy and 10 (7.4%) had pleurectomy. There were three (2.2%) patients who had pleurodesis.The median PFS was nine months (95% CI: 8.4 to 9.5 months) and the median OS was 12 months (95% CI: 11.3 to 12.6). Figures P = 0.036 and a HR = 0.21), CK7 (P = 0.016 and HR = 0.29), patients who received surgery (P = 0.001 and HR = 0.66), use of cisplatin versus carboplatin (P = 0.005 and HR = 0.25), use of pemetrexed/cisplatin versus other chemotherapy regimens (P = 0.001 and HR = −0.35), RECIST (P = 0.001 and HR = −0.29) and weight at the time of diagnosis (P = 0.002 and HR = −0.26). For OS the variables that demonstrated statistical significance were nuclear calretinin (P = 0.024 and HR = 0.23), cytoplasmic calretinin (P = 0.033 and HR = 0.22), CK7 (P = 0.012 and HR = 0.30), patients who received surgery (P = 0.001 and HR = 0.57), the use of cisplatin versus carboplatin (P = 0.011 and HR = 0.22), the use of pemetrexed/cisplatin versus other chemotherapy regimens (P = 0.001 and HR = −0.34), RECIST (P = 0.001 and HR = −0.30) and weight at the time of diagnosis (P = 0.002 and HR = −0.26). All these variables were positive in both one‐ and two‐tailed analysis. For PFS one‐tailed analysis, gender, nuclear calretinin, cytoplasmic calretinin and cytoplasmic WT1 also showed statistical significance . For OS, one‐tailed analysis, gender was also statistically significant (P = 0.026 and HR = 0.16).Univariate analysis showed statistical significance in median PFS for nuclear WT1 . After evaluation of patients, we found that the median OS in this trial, regardless of the chemotherapy regimen used, was similar to previous studies; 12 months compared with 12.7 months. For pemetrexed/cisplatin the median OS was 10 months compared to 12.1 months in the Vogelzang Phase III study.To evaluate the objective response, we used the RECIST 1.1 criteria. Independently of the chemotherapy regimen administered, 18.4% had a partial response, 7.4% had a complete response, 61.8% had stable disease and 12.5% had progression which was similar to the results reported in previous studies.P = 0.036 and a HR = 0.21) and CK7 (P = 0.016 and HR = 0.29). For OS, nuclear calretinin (P = 0.024 and HR = 0.23), cytoplasmic calretinin (P = 0.033 and HR = 0.22) and CK7 (P = 0.012 and HR = 0.30) showed statistical significance.Of all the immunohistochemical biomarkers, those which had an impact on prognosis for PFS were nuclear WT1 . We found a statistically significant difference in the use of cisplatin versus carboplatin, carboplatin being the chemotherapy agent that showed the most benefit in OS and PFS in patients with a 78% and 75% less risk, respectively . For chemotherapy , for OS, we found that there was a 66% greater risk of a worse prognosis when it was not received and a faster progression (70% more risk), therefore, the use of chemotherapy is a protective factor. On the other hand, the lower the response according to RECIST , the greater the probability of an unfavorable evolution of the disease . Likewise, low weight at the time of diagnosis was found to be a risk factor for disease with a poor prognosis at 74% for both PFS and OS . For the multivariate analysis of PFS, the same statistically significant variables were evaluated, RECIST being the only one with a tendency towards significance . For OS, the same statistically significant variables from the univariate study were also evaluated, showing RECIST as the only one which was statistically significant .For the treatments used in our patients, those who received surgery showed an improvement in PFS and OS with 34% and 43% less risk, respectively  and pemetrexed regimen, as demonstrated by the EMPHASIS study. Although an extended benefit in the use of bevacizumab in addition to pemetrexed‐cisplatinum has been previously reported in the literature, patients in our country, and specifically in our institution, are unable to afford this treatment. Exclusively for the benefit of PFS, the presence of WT1 and CK7 was associated with a better prognosis and OS for nuclear and cytoplasmic calretinin. With regard to the adverse factors of poor prognosis already known in the biphasic and sarcomatoid subtypes, we found a negative impact of not using the first‐line scheme with carboplatin and pemetrexed, as this combination treatment had the greatest impact on both PFS and OS.In conclusion, malignant pleural mesothelioma is a cancer with a poor prognosis usually diagnosed at an advanced stage of disease. The most determining prognostic factors for OS and PFS are cell differentiation, measured by immunohistochemical biomarkers, the treatment chosen, and RECIST, this being the most significant.The authors declare that there are no conflicts of interest.


Reliable, affordable and available identification methods are required to improve understanding of their significance in human illness. We examined the potential for MALDI-TOF MS, increasingly used in routine laboratories, for this task. Nineteen well-characterised strains were examined using a widely used MALDI-TOF MS commercial system, however only one strain confidently identified using their database. Data mining of the spectra obtained revealed a number of markers that could be used to help discriminate these genomospecies. We conclude that careful application of MALDI-TOF analysis could be useful to determine the role and significance of diverse C. concisus genomospecies in human disease.Strains identified as  This meC. concisus genomospecies, and explores the potential for enhanced discrimination using this method.This paper examines the performance of a commercial MALDI-TOF MS identification system for strains assigned to each of the two major 22.1Strains examined and their sources are listed in 2.22, 10% CO2, 3% O2, 7% H2) in a dedicated workstation  on 5% blood agar. MALDI-TOF MS profiling was performed using a Flex Biotyper instrument . Discrete samples of bacterial growth were smeared onto the steel analysis plate and 1 µl of 70% formic acid added before addition of the matrix solution; samples were air dried before analysis, as described previously (n = 6903 as of this study), as follows. Highly probable species identification (2.3-3.0); secure genus identification, probable species identifications (2.0-2.299); probable genus identification (1.7-1.999); or not reliable identification (0-1.699). Samples were compared with the Bruker database on 7th October 2020.Strains were cultured for 3 days under microaerobic conditions  for analysis. Cluster analysis was performed using the Peak based-Dice coefficient using the parameters of minimum height 0%, peak matching of constant tolerance 1, linear tolerance 500 ppm, shift factor 1, and UPGMA (unweighted-pair group method with arithmetic mean) algorithm.p-value < 0.05 were initially selected and further considered as the potential biomarker, combined with visual observation.The potential biomarkers were identified using the matrix mining tool according to the BioNumerics Tutorial “Peak matching and follow up analysis of spectra”. The peak matching was performed using default settings . All peak classes with a 33.1C. concisus was consistently confidently  identified to this species, and this was the only strain we tested that is present in the Bruker database. Of the remaining C. concisus genomospecies 1 strains, 45.7% of samples were considered probable species identifications and 13.5% probable genus identifications, in each case with C. concisus named as the most likely species. Genomospecies 2 strains yielded less definitive results, with 55.1% samples considered probable to species level, and 39.6% considered probable to genus level, again with C. concisus named as the most likely species. However, 5.1% of samples were not identified to any defined species (The range of identification scores for each of the MALDI-TOF sample replicates for the strains examined is summarised in  species .3.2Two major clusters were formed at the 44% similarity level . The fir3.34C. concisus genomospecies has been well documented (The genotypic variability of the cumented  and likecumented . The varcumented . In thiscumented .C. concisus, including the type strain examined in our study. The genomospecies designations of the other strains is not known and clearly do not represent the full diversity of C. concisus phenotypes, since 18 of our 19 isolates did not achieve convincing identification scores. Such performance can easily be improved by incorporating our data into the proprietary database and the manufacturer has a standard protocol by which this can be achieved.As of 7th October 2020, the Bruker identification database contained 14 strains of C. concisus genomospecies in gastrointestinal disease and potential zoonotic infection has long been difficult to resolve given the problems in routinely identifying them. It is hoped this study provides some insights into the use of an increasingly available tool, MALDI-TOF MS, for achieving this aim.The role of The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.