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In this paper we develop predictions from models of life-long demographic heterogeneity. These predictions are then compared to observations of mortality in large laboratory populations of Drosophila melanogaster. We find that the demographic heterogeneity models either require levels of variation that far exceed what would be considered biologically plausible, or they predict a much larger number of very old individuals than we actually observe. We conclude that the demographic heterogeneity models are not reasonable explanations of demographic patterns and are weakly motivated biological models.

Human immunodeficiency virus (HIV)-1 transmitted drug resistance in the drug-naïve population is of growing relevance in Estonia, where the number of antiretroviral (ARV) treatment-experienced subjects has been exponentially increasing during the last 10 y. The aim of this study was to estimate the rate of transmitted drug resistance among newly diagnosed subjects in Estonia in 2008. Genotypic resistance testing for viral genomic RNA was conducted for 201 subjects tested HIV-positive between 1 April and 30 November 2008. Of 145 genotyped viral strains in newly diagnosed patients, 123 were CRF06_cpx, 2 were subtype A1 and 3 were subtype B; in 17 cases viral sequences revealed recombinant structures similar to CRF06_cpx, subtype A1 and CRF02_AG. Resistance mutations were found in 8 (5.5%) virus strains, and 3 strains were resistant to at least 2 ARV classes. A total of 2.8% of sequences harboured mutations indicating nucleoside/nucleotide reverse transcriptase inhibitor resistance (M41L, M184V, M184I, T215C and T215D), 2.1% non-nucleoside reverse transcriptase inhibitor resistance (K103N, P225H) and 2.8% protease inhibitor resistance (M46I, L90M). These data suggest the need to extend genotypic HIV-1 drug resistance testing to newly diagnosed HIV-positive subjects to prevent potential ARV treatment failure. [ABSTRACT FROM AUTHOR]

Purpose: We aimed to describe SARS-CoV-2 lineages and diversity in children and adults in Estonia and similarity to travel-related cases and neighbouring countries., Methods: SARS-CoV-2 sequences in 2021-2022 from a nationwide study were included. The proportion of predominant lineages in Estonian regions and among travel-related cases was described by multinomial logistic regression. Simpson's indices of diversity were compared using linear regression. Dynamics of Bray-Curtis dissimilarity was described by applying fuzzy clustering to non-metrical dimensional scaling results., Results: A total of 2,630 sequences from children (<15 years) and 23,031 from adults (≥15 years) were included. The increase in the proportion of Alpha/Delta/Omicron BA.1/BA.2 lineages was delayed in smaller regions (by 3.5-27.5 days). The proportion of Alpha/Delta/Omicron BA.1 increased earlier among travel-related (n = 4,654) than non-travel-related cases (10.5 days). Diversity was lower in non-travel-related than travel-related cases until Delta period by 0.066. Dynamics of lineages and diversity were similar in adults and children. Similarity of lineages was delayed compared to Finland during Alpha/Omicron BA.1/BA.2 periods and different from all neighbouring countries during Delta period., Conclusion: SARS-CoV-2 lineages in children and adults were similar. Differences between regions and travel-related cases and varying similarity to neighbouring countries suggest the importance of mobility in the spread., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Soeorg et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: The COVID-19 pandemic was characterised by rapid waves of disease, carried by the emergence of new and more infectious SARS-CoV-2 virus variants. How the pandemic unfolded in various locations during its first two years has yet to be sufficiently covered. To this end, here we are looking at the circulating SARS-CoV-2 variants, their diversity, and hospitalisation rates in Estonia in the period from March 2000 to March 2022., Methods: We sequenced a total of 27,550 SARS-CoV-2 samples in Estonia between March 2020 and March 2022. High-quality sequences were genotyped and assigned to Nextstrain clades and Pango lineages. We used regression analysis to determine the dynamics of lineage diversity and the probability of clade-specific hospitalisation stratified by age and sex., Results: We successfully sequenced a total of 25,375 SARS-CoV-2 genomes (or 92%), identifying 19 Nextstrain clades and 199 Pango lineages. In 2020 the most prevalent clades were 20B and 20A. The various subsequent waves of infection were driven by 20I (Alpha), 21J (Delta) and Omicron clades 21K and 21L. Lineage diversity via the Shannon index was at its highest during the Delta wave. About 3% of sequenced SARS-CoV-2 samples came from hospitalised individuals. Hospitalisation increased markedly with age in the over-forties, and was negligible in the under-forties. Vaccination decreased the odds of hospitalisation in over-forties. The effect of vaccination on hospitalisation rates was strongly dependent upon age but was clade-independent. People who were infected with Omicron clades had a lower hospitalisation likelihood in age groups of forty and over than was the case with pre-Omicron clades regardless of vaccination status., Conclusions: COVID-19 disease waves in Estonia were driven by the Alpha, Delta, and Omicron clades. Omicron clades were associated with a substantially lower hospitalisation probability than pre-Omicron clades. The protective effect of vaccination in reducing hospitalisation likelihood was independent of the involved clade., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Päll et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Competing Interests: The authors report no conflicts of interest.

Introduction: This study aims to describe injury patterns, prehospital interventions and mortality rates of combat-related thoracic injuries during the past decade among Israel Defense Forces (IDF) soldiers before and after implementation of the 2012 IDF-Military Corps 'My Brother's Keeper' plan which included the publication of clinical practice guidelines (CPGs) for thoracic injuries, emphasis on adequate torso protection, introduction of modern life-saving procedures and encouragement of rapid evacuation., Methods: The IDF prehospital trauma registry was reviewed to identify all patients who sustained thoracic injuries from January 2006 to December 2017. IDF soldiers who were injured, died of wounds or killed in action (KIA) were included. These were cross-referenced with the Israel National Trauma Registry. The periods before and after the plan were compared., Results: 458 (12.3%) of 3733 IDF soldiers wounded on the battlefield sustained combat-related thoracic injuries. The overall mortality was 44.3% before the CPG and 17.3% after (p<0.001). Most were KIA: 97% (95 of 98) died by 30 June 2012, and 83% (20 of 24) after (p<0.001). Casualties treated with needle thoracostomy before and after CPG were 6.3% and 18.3%, respectively (p=0.002). More tube thoracostomies were performed after June 2012 (16.1% vs 5.4%, p=0.001). Evacuation was faster after June 2012 (119.4 min vs 560.8 min, p<0.001), but the rates of casualties evacuated within 60 min were similar (21.1% vs 25%, p=0.617)., Conclusions: Among military casualties with thoracic injuries, the rate of life-saving interventions increased, evacuation time decreased and mortality dropped following the implementation of My Brother's Keeper plan., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: In Eastern Europe, HIV-1 transmitted drug resistance (TDR) data, especially in the integrase (IN) region, are limited. In Estonia, INSTI (integrase strand transfer inhibitors) TDR has been studied only prior to the INSTI scale-up in late 2010s. The current study aimed to determine the levels of protease (PR), reverse transcriptase (RT) and IN surveillance drug resistance mutations (SDRMs) among newly diagnosed patients in Estonia in 2017., Methods: The study included 216 newly diagnosed HIV-1 individuals from 1 January until 31 December 2017 in Estonia. Demographic and clinical data were obtained from the Estonian Health Board, the Estonian HIV Cohort Study (E-HIV) and clinical laboratories' databases. The PR-RT and IN regions were sequenced and analysed for SDRMs and subtype determination., Results: Seventy-one percent (151/213) of available HIV-positive samples were successfully sequenced. The overall level of TDR was 7.9% (12/151; 95% CI 4.4%-13.8%); no dual or triple class resistance was detected. No major INSTI mutations were found. The distribution of SDRMs for NNRTI, NRTI and PI was 5.9% (9/151), 1.3% (2/151) and 0.7% (1/151), respectively. The predominant NNRTI mutation was K103N. CRF06&#95;cpx was the predominant variant (59%) in the Estonian HIV-1 population, followed by subtype A (9%) and subtype B (8%)., Conclusion: Although no major INSTI mutations were found, close monitoring of INSTI SDRMs is needed considering the extensive use of the first- and second-generation INSTIs. PR-RT TDR is slowly rising in Estonia, indicating the need for continuous surveillance in the future. Low genetic barrier NNRTIs should be avoided in the treatment regimens., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Purpose: To assess the prevalence of Cystoid macular edema (CME) in children with early onset retinal dystrophies (EORD) and to evaluate if there are associated factors and/or response to early treatment., Methods: Consecutive, retrospective case series. Medical records of patients, 18 years or younger, diagnosed with EORD were included in the study. Optic coherence tomography (OCT) scans, clinical and genetic characteristics as well as other associated factors were analyzed. Main outcome was the presence of CME on OCT scans ., Results: One hundred and two children with EORD (aged 1-18 years, mean 9.7 ± 4.2) were recruited. OCT was performed in 60/102 and among them, 19/60 had CME (31.7%). The disease-causing gene was identified in 13 children with CME; autosomal-recessive inheritance was found in 88.3% of those with an identified genotype. Children with Usher syndrome had CME in 44.4% of the cases. Early treatment of CME resulted in variable response., Conclusions: Our results show that 31.7% of children with EORD who underwent OCT have macular edema. CME prevalence was found to be relatively higher in children with Usher syndrome. Autosomal recessive was the most prevalent inheritance identified in the EORD group as well as in the CME group. Additional prospective research is needed to assess the efficacy of early CME treatment in pediatric EORD patients.

Background: Chest trauma is among the most common types of trauma, corresponding to 10% of trauma patients admitted to hospitals. In the military setting, thoracic trauma was reported as a significant cause of death. With well-timed treatment, chest trauma is regarded as survivable. Emergency thoracotomy (ET) is considered when the patient with trauma to the chest needs immediate resuscitation. Survival rate is reported as low as 1% in some reports and 20% in others. The survival rate depends on injury mechanism, protocols for intervention, and other decompressive procedures., Objectives: To determine parameters that may impact survival of ET., Methods: We conducted a retrospective cohort study to compare prehospital and in-hospital data regarding ET in the emergency department (ED) versus the operating room (OR)., Results: Between 2009 and 2017, 6532 casualties presented to the ED; 1125 with trauma to the chest. Fifty-four of those with chest trauma underwent ET in the hospital (4.8%), 22 (41%) in the ED, and 32 (59%) in the OR. The overall mortality of the ET subgroup was 48%. With regard to thoracotomies, 19/22 of patients (86%) who underwent ET in the ED died compared to 2/28 in the OR (13%)., Conclusions: Utilizing ET after chest trauma with appropriate clinical indications, well-trained personnel, and prompt transportation poses a significant challenge, but may be associated with better survival than that reported previously with military casualties. Adoption of indications and timed allocation to the OR may improve outcomes with chest trauma casualties.

A 70-year-old woman was urgently referred for neuro-ophthalmic evaluation when a routine visual field test demonstrated a pattern of bilateral nasal hemianopia. Detailed inspection of the visual field study revealed the hemianopias to be artifactual for the following reasons: (1) it was performed with an excessive number of false positive responses; (2) the grey scale plot had white patches, consistent with abnormally high sensitivity; (3) the total deviation probability maps were normal, indicating that no tested points had poor scores. Confrontational visual field testing was normal in all zones for both eyes. Repeated visual field testing showed no evidence of a true hemianopia. Even automated visual fields with highly specific abnormalities can merely be testing artifact. Scrutinize all components of the report before determining the clinical implications., Competing Interests: The authors report no conflict of interest., (Copyright © 2022 by S. Karger AG, Basel.)

Objectives: The large volume of scientific publications and the increasing emphasis on high-quality evidence for clinical decision-making present daily challenges to all clinicians, including thoracic surgeons. The objective of this study was to evaluate the contemporary trend in the level of evidence (LOE) for thoracic surgery clinical research., Methods: All clinical research articles published between January 2010 and December 2017 in 3 major general thoracic surgery journals were reviewed. Five authors independently reviewed the abstracts of each publication and assigned a LOE to each of them using the 2011 Oxford Centre for Evidence-Based Medicine classification scheme. Data extracted from eligible abstracts included study type, study size, country of primary author and type of study designs. Three auditing processes were conducted to establish working definitions and the process was validated with a research methodologist and 2 senior thoracic surgeons. Intra-class correlation coefficient was calculated to assess inter-rater agreement. Chi-square test and Spearman correlation analysis were then used to compare the LOE between journals and by year of publication., Results: Of 2028 publications reviewed and scored, 29 (1.4%) were graded level I, 75 (3.7%) were graded level II, 471 (23.2%) were graded level III, 1420 (70.2%) were graded level IV and 33 (1.6%) were graded level V (lowest level). Most publications (94.9%) were of lower-level evidence (III-V). There was an overall increasing trend in the lower LOE (P < 0.001). Inter-rater reliability was substantial with 95.5% (95%, confidence interval: 0.95-0.96) level of agreement between reviewers., Conclusions: General thoracic surgery literature consists mostly of lower LOE studies. The number of lower levels of evidence is dominating the recent publications, potentially indicating a need to increase the commitment to produce and disseminate higher-level evidence in general thoracic surgery., (© The Author(s) 2021. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Purpose: To describe a unique case of cystoid macular edema associated with Ibrutinib treatment for Chronic Lymphocytic Leukemia (CLL)., Observations: A 73-year-old male patient presented to the ophthalmology clinic complaining of decreased vision in his seeing-eye ('only eye', left). Further clinal examination and imaging revealed the presence of a cystoid macular edema (CME). With no apparent cause to this condition, topical treatment with NSAIDS and steroids continued over two years with only partial response and persistent macular edema, resulting in decreased vision. Cessation of Ibrutinib treatment resulted in resolution of the macular edema and improvement in visual acuity over 6 months., Conclusions and Importance: Several novel oncologic therapies have been associated with CME in recent years. This case demonstrates an association between Ibrutinib an oral, irreversible inhibitor of Bruton's Tyrosine Kinase (BTK), and the development of CME. CME was resistant to topical treatment but resolved after treatment cessation. Along with two previous cases reported, this case suggests that CME is a rare adverse event of Ibrutinib therapy. Screening for CME in Ibrutinib treated patients who report visual symptoms should be considered., Competing Interests: The authors report no conflict of interest., (© 2022 The Authors. Published by Elsevier Inc.)

Optic neuropathy can occur secondary to nutritional deficiencies in patients who have undergone bariatric surgery. We present a unique case of a 39-year-old man, claiming to be generally healthy, who presented with intermittent vertical diplopia and bilateral decreased vision in each eye. Visual acuity was 6/18 in the right eye and 6/12 in the left eye. Ishihara testing was defective for both eyes. Automated visual fields showed a severe generalized reduction in sensitivity in both eyes. The patient had a left head tilt and a right intermittent hypertropia of 30 prism diopters in primary position. CT of the orbits revealed a right superior oblique of small caliber. On further questioning, the patient admitted to a history of bariatric surgery 7 years prior to presentation with failure to take any nutritional supplements. Blood work demonstrated deficiencies in folate, thiamine, and copper. Within 6 months of initiating nutritional supplements, the vision in each eye was markedly improved and the diplopia resolved. There was an associated normalization of thiamine and copper, but folate levels remained low. We believe that the nutritional deficiency caused a bilateral optic neuropathy and the resulting vision loss precipitated a manifestation of a congenital superior oblique palsy that had previously just been a phoria. The case emphasizes the importance of considering occult sensory etiologies of acquired strabismus., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 by The Author(s). Published by S. Karger AG, Basel.)

Background: Estonia has a typical Eastern European HIV epidemic where the most frequent co-infection is chronic hepatitis C (HCV). We aimed to describe the changes in HCV prevalence, the distribution of HCV genotypes (GT), and HCV treatment in Estonian people living with HIV over 15 years., Methods: We used data of subjects included to the Estonian HIV Cohort Study (E-HIV) before 31st of December 2015. We compared two time periods-first, 1st of January 2000 to 31st of December 2008 when the HIV epidemic was mostly spreading among people who inject drugs (PWID) and second, 1st of January 2009 to 31st of December 2015 when HIV started to emerge to the general population., Results: Of 4422 HIV positives 3708 (84%) had information about their HCV serostatus; 2706 (61%) were HCV seropositive, of latter 1625 (60%) were HCV RNA positive, 239 (9%) had their HCV GT determined, and 141 (5%) received treatment for HCV. The dominating subtypes were 1b (42%) and 3a (37%) followed by 1a (16%), and the few cases of 2 (1.5%). HCV prevalence was 1.5 times (95% CI 1.4-1.6) higher in subjects diagnosed with HIV in first as compared to those diagnosed in second period (84% vs 56%, respectively). There were more men and the median age at HIV diagnosis was lower in HIV/HCV co-infected than in HIV mono-infected patients (70% vs 47% and 24 years vs. 30 years, respectively; both p < 0.001)., Conclusion: There is a decrease in HCV prevalence but it remains high among HIV positive PWID, suggesting that there is need for improvement of harm reduction programs among PWID., (© 2021. The Author(s).)

Lung cancer remains the leading cause of cancer death worldwide despite the significant progress made by immune checkpoint inhibitors, including programmed death receptor-1 (PD1)/PD ligand 1 (PDL1)-blockade therapy. PD1/PDL1-blockade has achieved unprecedented tumor regression in some patients with advanced lung cancer. However, the majority of patients fail to respond to PD1/PDL1 inhibitors. The high rate of therapy non-response results from insufficient PDL1 expression on most patients' tumors and the presence of further immunosuppressive mechanisms in the tumor microenvironment. Here, we sensitize non-responding tumors from patients with lung cancer to PD1-blockade therapy using highly cytotoxic expanded natural killer (NK) cells. We uncover that NK cells expanded from patients with lung cancer dismantle the immunosuppressive tumor microenvironment by maintaining strong antitumor activity against both PDL1+ and PDL1- patient tumors. In the process, through a contact-independent mechanism involving interferon γ, expanded NK cells rescued tumor killing by exhausted endogenous TILs and upregulated the tumor proportion score of PDL1 across patient tumors. In contrast, unexpanded NK cells, which are susceptible to tumor-induced immunosuppression, had no effect on tumor PDL1. As a result, combined treatment of expanded NK cells and PD1-blockade resulted in robust synergistic tumor destruction of initially non-responding patient tumors. Thus, expanded NK cells may overcome the critical roadblocks to extending the prodigious benefits of PD1-blockade therapy to more patients with lung cancer and other tumor types., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: We aim to show the feasibility of using an integrated prevention and care continuum (PCC) model as a complete and improved tool for HIV control measurement and programming. Alignment of prevention and care continua is essential to further improve health outcomes and minimize HIV transmission risk., Design: Cross-sectional study., Methods: Data from 977 persons who inject drugs (PWID) collected in 2011-2016 in Tallinn, Estonia, were used to construct an HIV PCC for PWID, stratified by risk for acquiring or transmitting HIV infection and by coverage of combined interventions. We also estimated the average protective effect of current levels of intervention provision., Results: 74.4%, 20.3% and 35.2% of PWID were currently using needle and syringe programmes (NSP), drug treatment and HIV testing, respectively. 51.1% of current PWID were HIV seropositive and of those 62.5% were currently on ART and 19.0% were virally suppressed. Across the PCC, individuals moved between categories of being aware and ever using drug treatment (resulting in -50% "leakage"); from ever having used to currently using drug treatment (-59%); between "ever testing" and "current (continuous) testing" (-62%); and from self-reported antiretroviral therapy (ART) adherence to viral suppression (-70%). Use of prevention services was higher among those at risk of transmission (HIV positive). The overall reduction in acquisition risk among HIV-negative PWID was 77.7% (95% CrI 67.8-84.5%), estimated by the modelled protective effects of current levels of NSP, drug treatment and ART compared to none of these services., Conclusions: Our findings suggest that developing a cohesive model for HIV prevention and treatment is feasible and reflects the bi-directional relationships between prevention and care. The integrated continuum model indicates the major factors which may predict the epidemic course and control response., Competing Interests: The authors have declared that no competing interests exist.

Knowledge of the outcomes of critically ill patients is crucial for health and government officials who are planning how to address local outbreaks. The factors associated with outcomes of critically ill patients with coronavirus disease 2019 (Covid-19) who required treatment in an intensive care unit (ICU) are yet to be determined., Methods: This was a retrospective registry-based case series of patients with laboratory-confirmed SARS-CoV-2 who were referred for ICU admission and treated in the ICUs of the 13 participating centers in Israel between 5 March and 27 April 2020. Demographic and clinical data including clinical management were collected and subjected to a multivariable analysis; primary outcome was mortality., Results: This study included 156 patients (median age = 72 years (range = 22-97 years)); 69% (108 of 156) were male. Eighty-nine percent (139 of 156) of patients had at least one comorbidity. One hundred three patients (66%) required invasive mechanical ventilation. As of 8 May 2020, the median length of stay in the ICU was 10 days (range = 0-37 days). The overall mortality rate was 56%; a multivariable regression model revealed that increasing age (OR = 1.08 for each year of age, 95%CI = 1.03-1.13), the presence of sepsis (OR = 1.08 for each year of age, 95%CI = 1.03-1.13), and a shorter ICU stay(OR = 0.90 for each day, 95% CI = 0.84-0.96) were independent prognostic factors., Conclusions: In our case series, we found lower mortality rates than those in exhausted health systems. The results of our multivariable model suggest that further evaluation is needed of antiviral and antibacterial agents in the treatment of sepsis and secondary infection.

An amendment to this paper has been published and can be accessed via the original article.

Background: The life expectancy of hemophiliacs is similar to that of the general population. As a result, the prevalence of age-related cardiovascular diseases has increased. We present our experience with hemophilia patients who underwent cardiac surgery in our Medical Center between 2004 and 2019., Methods: All hemophilia patients who underwent cardiac surgery were identified, and their peri-operative data evaluated retrospectively., Results: Ten patients were identified: six with hemophilia-A, one with hemophilia-B, and three with hemophilia-C (factor XI deficiency). Cardiac procedures included ten coronary artery bypass grafts and one aortic valve replacement. Hemophilia-A and B patients were treated with factor substitution, whereas patients with factor XI deficiency were treated with fresh frozen plasma. One patient died, and one patient suffered from non-active gastrointestinal bleeding., Conclusions: While major cardiac surgery can be performed safely on patients with hemophilia, a multidisciplinary team approach and strict postoperative monitoring are essential in order to achieve optimal results.

Background: Due to the widespread use of non-nucleoside reverse transcriptase inhibitors (NNRTI) as part of first-line therapies to curb the human immunodeficiency virus (HIV) epidemic in Eastern-European countries, transmitted drug resistance (TDR) is of serious concern in this region. Therefore, TDR and its associated risk factors were investigated among newly diagnosed HIV-1 subjects in Estonia., Methods: This nationwide observational study included all newly diagnosed HIV-1 subjects from January 1 until December 31, 2013. Demographic and clinical data were collected using the national surveillance system and the Estonian HIV-positive patient database (E-HIV). Starting from RNA, the HIV-1 protease (PR) and reverse transcriptase (RT) region was sequenced and surveillance drug resistance mutations (SDRM) were determined. Sequences from previous studies in Estonia and from public databases were included to study epidemic trends and to determine TDR clusters by phylogenetic analysis., Results: Out of 325 newly diagnosed HIV-1 infections, 224 were successfully sequenced (68%). As in previous studies from Estonia, the circulating recombinant form CRF06&#95;cpx was the most prevalent HIV subtype (164/224, 74%). Fifteen strains displayed SDRM, giving a TDR rate of 6.7% (95% CI 3.9; 11.0). The most common SDRMs were associated with NNRTI (10/15, 4.5%), followed by PI (3/15, 1.3%) and NRTI (2/15, 0.9%). K103 N (8/15, 53%) was the most common SDRM. The level of TDR and mutational patterns were comparable to previous years. Twenty-six transmission clusters containing Estonian sequences were observed, of which 23/26 belonged to CRF06&#95;cpx and 2/26 displayed evidence of TDR. The only risk factor associated with the presence of TDR was imprisonment (OR 5.187, CI 1.139-25.565, p = 0.034)., Conclusions: TDR remained stable at a moderate level in Estonia, K103N is the main SDRM with only one transmission-pair detected. We suggest screening for TDR at the time of diagnosis or prior to antiretroviral treatment initiation to tailor first-line regimens accordingly., Summary: The third consecutive transmitted drug resistance (TDR) study demonstrated a stable TDR in Estonia. TDR reached 6.7% (moderate level) in 2013, with imprisonment being the only associated risk factor. Few drug resistance-associated transmission clusters were identified., (Copyright © 2019 Elsevier B.V. All rights reserved.)

We investigated the presence of a single-nucleotide polymorphism designated rs12979860 in the interferon λ4 (IFNλ4) gene among 345 people who inject drugs (PWID) and 495 blood donors to evaluate associations between the rs12979860 genotypes and human immunodeficiency virus/hepatitis C virus (HIV/HCV). The rs12979860 TT genotype was over-represented among HIV+ PWID than HIV- PWID and blood donors (16% vs 8% and 10%, P = 0.03, respectively). PWID with TT genotype had approximately twice the probability of being HIV+ (odds ratio [OR], 2.19; 95% confidence interval [CI], 1.11 to 4.33) than PWID without TT. Every additional year of intravenous drug use (IVDU) decreased the OR 1.16 times (OR, 0.86; 95% CI, 0.75 to 0.98). This suggests that rs12979860 TT increases susceptibility to HIV and this impact decreases with increasing duration of IVDU., (© 2018 Wiley Periodicals, Inc.)

Background: This study assessed early and late clinical outcomes in patients who underwent aortic valve repair or an aortic valve-sparing operation and investigated predictors for failure., Methods: Of 227 consecutive patients who underwent aortic valve repair or a valve-sparing operation in our department between 2004 and 2016, 81 (36%) underwent aortic root replacement with or without cusp repair, 97 (42%) ascending aorta replacement with or without cusp repair, and 49 (22%) isolated aortic valve repair. Clinical and echocardiographic follow-up was complete., Results: One patient (0.4%) died in-hospital. Mean clinical and echocardiographic follow-up was 69 ± 40 months (range, 1 to 147 months) and 53 ± 40 months (range, 1 to 147 months), respectively. Fifteen patients (6.6%) died during follow-up, with an overall 5-year survival rate of 94.4%. Recurrent significant (≥3) aortic insufficiency developed in 20 patients (8.8%), 17 of whom underwent reoperation, with a 5-year freedom from reoperation rate of 88%. Predictors for recurrent significant aortic insufficiency or reoperation were greater preoperative aortic insufficiency (grade III to IV vs I to II; relative risk [RR], 1.97; p = 0.023), cusp repair (RR, 2.92; p = 0.001), higher European System for Cardiac Operative Risk Evaluation score (RR, 1.16; p = 0.006), and valve repair with pericardial patch augmentation (RR, 2.34; p = 0.032)., Conclusions: Aortic valve repair and valve-sparing operations can be performed with good early and late clinical outcomes. In our experience, however, the rate of recurrent aortic insufficiency was significant, especially in patients who underwent cusp augmentation with glutaraldehyde-treated autologous pericardial patch., (Copyright © 2018 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Adoptive cell therapy (ACT) of tumor infiltration lymphocytes (TIL) yields promising clinical results in metastatic melanoma patients, who failed standard treatments. Due to the fact that metastatic lung cancer has proven to be susceptible to immunotherapy and possesses a high mutation burden, which makes it responsive to T cell attack, we explored the feasibility of TIL ACT in non-small cell lung cancer (NSCLC) patients. Multiple TIL cultures were isolated from tumor specimens of five NSCLC patients undergoing thoracic surgery. We were able to successfully establish TIL cultures by various methods from all patients within an average of 14 days. Fifteen lung TIL cultures were further expanded to treatment levels under good manufacturing practice conditions and functionally and phenotypically characterized. Lung TIL expanded equally well as 103 melanoma TIL obtained from melanoma patients previously treated at our center, and had a similar phenotype regarding PD1, CD28, and 4-1BB expressions, but contained a higher percent of CD4 T cells. Lung carcinoma cell lines were established from three patients of which two possessed TIL cultures with specific in vitro anti-tumor reactivity. Here, we report the successful pre-clinical production of TIL for immunotherapy in the lung cancer setting, which may provide a new treatment modality for patients with metastatic NSCLC. The initiation of a clinical trial is planned for the near future.

Background: Unicuspid and bicuspid aortic valve (BAV) are congenital cardiac anomalies associated with valvular dysfunction and aortopathies occurring at a young age., Objectives: To evaluate our experience with aortic valve repair (AVr) in patients with bicuspid or unicuspid aortic valves., Methods: Eighty patients with BAV or unicuspid aortic valve (UAV) underwent AVr. Mean patient age was 42 ± 14 years and 94% were male. Surgical technique included: aortic root replacement with or without cusp repair in 43 patients (53%), replacement of the ascending aorta at the height of the sino-tubular junction with or without cusp repair in 15 patients (19%), and isolated cusp repair in 22 patients (28%)., Results: The anatomical structure of the aortic valve was bicuspid in 68 (85%) and unicuspid in 12 patients (15%). Survival rate was 100% at 5 years of follow-up. Eleven patients (13.7%) underwent reoperation, 8 of whom presented with recurrent symptomatic aortic insufficiency (AI). Late echocardiography in the remaining 69 patients revealed mild AI in 63 patients, moderate recurrent AI in 4, and severe recurrent AI in 2. Relief from recurrent severe AI or reoperations was significantly lower in patients who underwent cusp repair compared with those who did not (P = 0.05). Furthermore, the use of pericardial patch augmentation for the repair was a predictor for recurrence (P = 0.05)., Conclusions: AVr in patients with BAV or UAV is a safe procedure with low morbidity and mortality rates. The use of a pericardial patch augmentation was associated with higher repair failure.

The Micra transcatheter leadless pacemaker, a single-chamber leadless ventricular pacemaker, is implanted percutaneously through the femoral vein. We present the case of a patient in whom the Micra leadless pacemaker was implanted during valve surgery., (Copyright © 2018 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)