Five-Year Follow-Up of Health-Related Quality of Life in Differentiated Thyroid Cancer Patients Treated with Total Thyroidectomy and Radioiodine in Sweden: A Nationwide Prospective Cohort Study.

Background: Despite a good prognosis, survivors of differentiated thyroid cancer (DTC) may have reduced health-related quality of life (HRQOL) many years after treatment, and it is unclear how suppression of thyroid-stimulating hormone (TSH) may contribute to HRQOL. This study investigated changes in HRQOL in the 5 years following DTC treatment, the association between HRQOL and TSH suppression, and how HRQOL compares to the general population. Methods: In this nationwide prospective cohort study, 487 patients with DTC were identified between 2012 and 2017 from all Swedish hospitals treating patients with DTC. Patients treated with total thyroidectomy and planned for radioiodine answered the Swedish version of the Short Form-36 Health Survey (SF-36) and a study specific questionnaire at treatment and after 1, 3, and 5 years. Summary measures for physical and mental QOL were derived from the SF-36, and TSH values were collected from patient records. To study changes in HRQOL over time, linear mixed models were fitted on multiply imputed data, with all patients and measurement points included in the model. Results: In total, 351 patients consented to participate in the study. In the 5 years following DTC treatment, physical QOL did not change significantly with time, while mental QOL improved by on average 0.61 (p < 0.001) per year. TSH levels were not predictive of either physical or mental QOL, or their change over time. At 5 years, there was a significant difference in physical and mental QOL compared with the Swedish general population, but effect sizes were small (Cohen's d = 0.29 and -0.21, respectively). The SF-36 domains general health, vitality, social functioning, and mental health were lower at 5 years compared with the general population (difference 8.7-13.3), and these differences were clinically significant. Conclusions: The mental component of HRQOL improves over time following DTC treatment. HRQOL in patients with DTC is not explained by TSH suppression. Although overall differences in physical and mental HRQOL compared with the general population were small 5 years after treatment, several specific psychosocial HRQOL domains were clinically meaningfully reduced. Psychosocial health issues should be screened for during DTC follow-up.

User Drafts for the Design of an mHealth Application for Equestrians.

A study was conducted to find out user ideas for the design and workflow of an mHealth application supporting triage of horses by equestrians. Results focus on information input elements and also include some requirements for information.

Video versus direct laryngoscopy to improve the success rate of nasotracheal intubations in the neonatal intensive care setting: a randomised controlled trial.

OBJECTIVE: To assess whether video laryngoscopy (VL) for tracheal intubation of neonates results in a higher first-attempt success rate and fewer adverse tracheal intubation-associated events (TIAEs) when compared with direct laryngoscopy (DL). DESIGN: Single-centre, parallel group, randomised controlled trial. SETTING: University Medical Centre Mainz, Germany. PATIENTS: Neonates <440/7 weeks postmenstrual age in whom tracheal intubation was indicated either in the delivery room or in the neonatal intensive care unit. INTERVENTION: Intubation encounters were randomly assigned to either VL or DL at first attempt. PRIMARY OUTCOME: First-attempt success rate during tracheal intubation. RESULTS: Of 121 intubation encounters assessed for eligibility, 32 (26.4%) were either not randomised (acute emergencies (n=9), clinicians' preference for either VL (n=8) or DL (n=2)) or excluded from the analysis (declined parental consent (n=13)). Eighty-nine intubation encounters (41 in the VL and 48 in the DL group) in 63 patients were analysed. First-attempt success rate was 48.8% (20/41) in the VL group compared with 43.8% (21/48) in the DL group (OR 1.22, 95% CI 0.51 to 2.88).The frequency of adverse TIAEs was 43.9% (18/41) and 47.9% (23/48) in the VL and DL group, respectively (OR 0.85, 95% CI 0.37 to 1.97). Oesophageal intubation with concomitant desaturation never occurred in the VL group but in 18.8% (9/48) of intubation encounters in the DL group. CONCLUSION: This study provides effect sizes for first-attempt success rates and frequency of TIAEs with VL compared with DL in the neonatal emergency setting. This study was underpowered to detect small but clinically important differences between the two techniques. The results of this study may be useful in planning future trials.

[Changes in neonatal care : Implications for ophthalmological care]. / Wandel der neonatologischen Versorgung : Implikationen für die augenärztliche Versorgung.

BACKGROUND: Preterm infants are at risk of characteristic, sometimes life-threatening diseases and development of deficits related to immaturity. In the field of ophthalmology, retinopathy of prematurity (ROP) and vision impairment reflect structural and functional disturbances in this large group of patients. In high income countries, more and more very immature preterm infants survive into adolescence and adulthood. OBJECTIVE: To characterize the impact of an increasing number of surviving individuals born preterm on the provision of ophthalmological care in Germany. MATERIAL AND METHODS: A literature search and analysis of key figures and quality indicators published in national health registers were carried out. RESULTS: Currently, about 60,000 preterm infants are born in Germany every year. Of these, approximately 3600 extremely immature preterm infants with a gestational age < 28 weeks are treated with a curative approach on neonatal units. The survival rate is around 80%. A rise in the proportion of infants suffering from severe ROP has not been observed in recent years in Germany. The incidences of other structural and functional visual impairments vary between 3% and 25% in high income countries. CONCLUSION: The incidence of ROP apparently has not increased in Germany. However, specific peculiarities of the structure and function of the visual system of individuals born preterm have to be taken into account. Approximately 70,000 outpatient check-ups of infants and toddlers, who require both, ophthalmological and developmental neurological expertise, are estimated for Germany each year.

Early life adversity: Epigenetic regulation underlying drug addiction susceptibility.

Drug addiction is a leading cause of disability worldwide, with more than 70,000 Americans dying from drug overdose in 2019 alone. While only a small percentage of chronic drug users escalate to drug addiction, little is understood on the precise mechanisms of this susceptibility. Early life adversity is causally relevant to adult psychiatric disease and may contribute to the risk of addiction. Here we review recent pre-clinical evidence showing that early life exposure to stress and/or drugs regulates changes in behavior, gene expression, and the epigenome that persist into adulthood. We summarize the major findings and gaps in the preclinical literature, highlighting studies that demonstrate the often profound differences between female and male subjects.

Parental perceptions of informed consent in a study of tracheal intubations in neonatal intensive care.

Background and objective: Obtaining informed consent in neonatal emergency research is challenging. The aim of this study was to assess parental perceptions of informed consent following participation in a clinical trial in neonatal emergency care. Methods: This was a supplementary analysis of a randomised controlled trial comparing video and direct laryngoscopy for neonatal endotracheal intubation in the delivery room and neonatal intensive care unit. After obtaining informed consent for the clinical trial, parents were asked to answer a series of self-administered questions about their perceptions of clinical trial participation and the consent process. Informed consent had been given either before birth, after birth but before inclusion in the trial, or after inclusion in the trial. Results: We received responses from 33 mothers and 27 fathers (n = 60) of the 63 preterm and term infants who participated in the study. Fifty-three (89.8%, n = 59) parents agreed that infants should participate in clinical trials, and 51 (85%, n = 60) parents agreed that parents should be asked for informed consent. Fifty-three (89.8%, n = 59) parents felt that their infant's participation in this particular trial would be beneficial. Fifty-two (86.7%, n = 60) parents felt that the informed consent process was satisfactory. One parent (100%, n = 1) approached before birth, 23 parents (82.1%, n = 28) approached after birth but before enrolment and 26 (83.9%, n = 31) parents approached after enrolment were satisfied with the timing of the consent process. Eight (13.3%, n = 60) parents felt some pressure to provide informed consent. Of these, two (25%) were approached before enrolment and six (75%) were approached after enrolment. Conclusion: Parents valued their infant's participation in an emergency neonatal clinical trial and considered it important to be asked for consent. In this study, it seemed less important whether consent was obtained before or after the intervention. Future studies may need to investigate which form of consent is most acceptable to parents for the individual study in question.

Caries Experience and Increment in Children Attending Kindergartens with an Early Childhood Caries Preventive Program Compared to Basic Prophylaxis Measures-A Retrospective Cohort Study.

Dental caries constitutes a public health challenge. As preventive strategies are desirable, this retrospective cohort study aimed to assess the caries experience and increment in children attending kindergartens with an early childhood caries (ECC) preventive program (intervention group, IG) compared to basic prophylaxis measures (control group, CG) located in areas of different socioeconomic status (SES) within Marburg (Germany). The long-term caries experience (2009−2019) of these 3−5-year-old kindergarten children was evaluated. For the caries increment, dental records of 2019 were screened for the availability of a minimum of two dental examinations at least 8 months apart. Caries was scored according to the WHO criteria (dmf−t). The data were split by observation period (300−550 and >550 days). Overall, 135 children (Ø 3.7 years) attended IG, and 132 children (Ø 3.6 years) attended CG. After 300−550 days, no significant differences were found between both groups regarding mean caries increment and experience (p > 0.05). After >550 days, IG with low SES exhibited a high caries experience. Fluoride varnish applications could not reduce the caries increment compared to CG in the short-term but slightly decreased the long-term caries experience. Comprehensive ECC prevention measures actively involving parents are needed to overcome the caries burden.

Structure-function relationships of the disease-linked A218T oxytocin receptor variant.

Various single nucleotide polymorphisms (SNPs) in the oxytocin receptor (OXTR) gene have been associated with behavioral traits, autism spectrum disorder (ASD) and other diseases. The non-synonymous SNP rs4686302 results in the OXTR variant A218T and has been linked to core characteristics of ASD, trait empathy and preterm birth. However, the molecular and intracellular mechanisms underlying those associations are still elusive. Here, we uncovered the molecular and intracellular consequences of this mutation that may affect the psychological or behavioral outcome of oxytocin (OXT)-treatment regimens in clinical studies, and provide a mechanistic explanation for an altered receptor function. We created two monoclonal HEK293 cell lines, stably expressing either the wild-type or A218T OXTR. We detected an increased OXTR protein stability, accompanied by a shift in Ca2+ dynamics and reduced MAPK pathway activation in the A218T cells. Combined whole-genome and RNA sequencing analyses in OXT-treated cells revealed 7823 differentially regulated genes in A218T compared to wild-type cells, including 429 genes being associated with ASD. Furthermore, computational modeling provided a molecular basis for the observed change in OXTR stability suggesting that the OXTR mutation affects downstream events by altering receptor activation and signaling, in agreement with our in vitro results. In summary, our study provides the cellular mechanism that links the OXTR rs4686302 SNP with genetic dysregulations associated with aspects of ASD.

Characteristics of neonatal herpes simplex virus infections in Germany: results of a 2-year prospective nationwide surveillance study.

OBJECTIVE: To assess incidence and burden of neonatal herpes simplex virus (HSV) infections and to explore possible transmission routes. METHODS: A 2-year prospective nationwide surveillance study performed in 2017 and 2018. All German paediatric departments (n=464 in 2017, n=441 in 2018) were contacted on a monthly basis to report potential cases of neonatal HSV infections. Infants with a postnatal age of ≤60 days and a positive HSV PCR or HSV culture from skin, mucous membrane, vesicles or conjunctival smear, blood or cerebrospinal fluid were included in the study. RESULTS: 37 cases were analysed. 29 patients who exhibited no or only mild clinical symptoms were discharged home without organ damage or neurological abnormalities. Four patients showed significant neurological impairment, one patient required liver transplantation and two patients died during in-patient treatment. The 2-year incidence of neonatal HSV infections was 2.35 per 100 000 live births (95% CI 1.69 to 3.02) and disease-specific mortality was 0.13 per 100 000 live births (95% CI 0.04 to 0.21). Data on possible transmission routes were available in 23 cases. In 20 cases, an orofacial HSV infection was present in one or more family members. An active maternal genital HSV infection was reported in 3 cases. CONCLUSION: Neonatal HSV infections are rare in Germany. Most infants have a benign clinical course, but some infants are severely affected. Postnatal HSV exposure may account for a considerable number of neonatal HSV infections.

Long-term microtensile bond strength of self-etch adhesives and influence of 7-s phosphoric acid etching on adhesion of a 3-step etch-and-rinse adhesive to the dentine of primary teeth.

BACKGROUND: The immediate microtensile bond strength (µTBS) of self-etch (SE) adhesives to primary dentine is promising, but evidence about the durability is scarce. AIM: To assess the long-term µTBS of SE adhesives to primary dentine and to examine the effect of 7-s etching on µTBS of a 3-step etch-and-rinse (ER) adhesive. DESIGN: The enamel of 115 caries-free human primary teeth was ground flat, and bonding was performed according to group assignment: G-aenial™ Bond/GC [GB], Clearfil™ SE Bond/Kuraray [CS], OptiBond™ XTR/Kerr [OX], Scotchbond™ Universal/3M™ [SU], Prime&Bond® NT™/Dentsply [PB], and OptiBond™ FL/Kerr [OF]. After storage (24 h, 6 mos., 12 mos.), 1,762 beams were cut for µTBS testing. Fracture analysis was performed using light/fluorescence microscopy. Resin-dentine interfaces were exemplarily analyzed using SEM. RESULTS: After 24 h, OX and SU showed significantly higher estimated mean µTBS than GB, which exhibited the lowest µTBS at all stages (p < .05). µTBS within each adhesive group showed slight variations over time (p > .05). OF_SE produced acceptable µTBS. Etching increased the mean immediate µTBS for OF (p > .05) and the percentage of cohesive fractures. CONCLUSIONS: SE adhesives achieved durable µTBS to primary dentine. 7-s etching may improve the immediate µTBS of a 3-step ER adhesive.

Longitudinal Study of the Signal Strength in two Serologic Assays for Detection of SARS-CoV-2 Specific Antibodies.

BACKGROUND: In the course of the current SARS-CoV-2 pandemic, antibody assays provide an important means for guidance of public health efforts. Thus, characterization of the course of antibody signals on different widely used assays is needed. METHODS: We selected 25 PCR-confirmed SARS-CoV-2 cases among 3,273 healthcare workers and measured the course of the antibody signal using the Abbott Architect SARS-CoV-2 IgG assay and the Roche Elecsys® Anti-SARS-CoV-2 immunoassay. The signal strength was then modelled using linear mixed models adjusted for age. RESULTS: Since first sampling, the assay signal decreased per day in the Abbott assay (standardized slope (ß) = -0.46, 95% CI = -0.54 to -0.39). In contrast, an increase in the signal was ascertained by the Roche immunoassay per day (ß = 0.25, 95% CI = 0.09 to 0.41). CONCLUSIONS: Roche Elecsys® Anti-SARS-CoV-2 immunoassay may exhibit greater sensitivity in detecting SARS-CoV-2-specific antibodies in individuals in late stages of postinfection.

Post-Fatigue Fracture and Marginal Behavior of Endodontically Treated Teeth: Partial Crown vs. Full Crown vs. Endocrown vs. Fiber-Reinforced Resin Composite.

OBJECTIVES: To investigate in vitro post-fatigue fracture behavior of endodontically treated molars having been differently restored. METHODS: A total of 120 extracted human molars were used. A total of 120 specimens in 14 test groups and one control group (n = 8) were root canal treated. After postendodontic sealing and build-up (AdheSE Universal, SDR), additional MOD preparations were cut. Postendodontic restorations were: Direct restorations (Tetric EvoCeram BulkFill bonded with AdheSE Universal and EverX Posterior/Essentia bonded with G-Premio Bond; as filling (F) or direct partial crown (DPC) after reducing the cusps 2 mm; indirect adhesive restorations (partial crown/PC vs. full crown/FC): e.max CAD, Celtra Duo, both luted with Variolink Esthetic; indirect zirconia restorations (partial crown/PC vs. full crown/FC), luted with RelyX Unicem 2; indirect non-bonded cast gold restorations (partial crown/PC vs. full crown/FC; Degunorm), luted with Ketac Cem. Before and after 300,000 thermocycles (5/55 °C) and 1.2 Mio. A total of 100 N load cycles, replicas were analyzed under a SEM for marginal quality in enamel and dentin (where applicable) and finally, specimens were loaded until fracture. RESULTS: In direct groups, there was no difference between RC and FRC in fracture strength (p > 0.05); however, direct partial crowns showed higher post-fatigue fracture resistance. Regarding marginal quality, intracoronal FRC restorations exhibited more gap-free margins in enamel than RC. In the indirect groups, there was no significant difference between partial and full crowns in any of the adhesively luted ceramic groups regarding post-fatigue fracture resistance. Zirconia partial crowns exhibited significantly lower marginal quality in enamel. Indirect groups performed significantly better than direct groups in fracture resistance. Within the indirect restorations, both cast gold groups and zirconia full crowns exhibited the highest fracture resistance being superior to control teeth. SIGNIFICANCES: Within the limits of this in vitro investigation, it can be concluded that any kind of indirect restoration with cusp replacement is suitable for ETT restoration when a certain cavity extension is exceeded. All indirect restorations, i.e., endocrowns, partial crowns, and full crowns showed a promising performance after in vitro fatigue-loading.

Dental Education during the COVID-19 Pandemic in a German Dental Hospital.

Due to the SARS-CoV-2 pandemic, dental treatment performed by undergraduate students at the University of Marburg/Germany was immediately stopped in spring 2020 and stepwise reinstalled under a new hygiene concept until full recovery in winter 2020/21. Patient treatment in the student courses was evaluated based on three aspects: (1) Testing of patients with a SARS-CoV-2 Rapid Antigen (SCRA) Test applied by student assistants (SA); (2) Improved hygiene regimen, with separated treatment units, cross-ventilation, pre-operative mouth rinse and rubber dam application wherever possible; (3) Recruitment of patients: 735 patients were pre-registered for the two courses; 384 patients were treated and a total of 699 tests with the SCRA test were performed by SAs. While half of the patients treated in the course were healthy, over 40% of the patients that were pre-registered but not treated in the course revealed a disease being relevant to COVID (p < 0.001). 46 patients had concerns to visit the dental hospital due to the increase of COVID incidence levels, 14 persons refused to be tested. The presented concept was suitable to enable patient treatment in the student course during the SARS-CoV-2 pandemic.

[Amalgam and alternatives-discussions on mercury reduction in the environment]. / Amalgam und Alternativen ­ Diskussionen zur Quecksilberreduktion in der Umwelt.

Dental amalgam has been successfully used for the restoration of carious lesions for more than 180 years. It is clinically characterized by high longevity and low technique sensitivity. For decades, dental amalgam has been discussed in the public, especially due to its roughly 50% mercury content. Since the Minamata Convention was published in 2013 with the primary goal of reducing the anthropogenic mercury release into the environment, the previously muted amalgam discussion has received fresh impetus. Another considerable disadvantage of amalgam is its silver/greyish color, which simply no longer matches patients' esthetic demands.The present paper describes the basic problems with amalgam against the background of multiple biological, clinical, and health policy factors. Possible consequences of the Minamata Convention concerning legal regulations as well as the use of dental biomaterials and therefore also relating to the future national healthcare system are discussed. Finally, possible amalgam alternatives and the urgent need for biomedical research towards restorative dentistry are presented, embedded into the crucial question of whether we are actually conducting the correct debate.

Adverse Events and Unsuccessful Intubation Attempts Are Frequent During Neonatal Nasotracheal Intubations.

Background: Intubation of neonates is difficult and hazardous. Factors associated with procedure-related adverse events and unsuccessful intubation attempts are insufficiently evaluated, especially during neonatal nasotracheal intubations. Objective: Aim of this study was to determine the frequency of tracheal intubation-associated events (TIAEs) during neonatal nasotracheal intubations and to identify factors associated with TIAEs and unsuccessful intubation attempts in our neonatal unit. Methods: This was a prospective, single-site, observational study from May 2017 to November 2019, performed at a tertiary care neonatal intensive care unit in a German academic teaching hospital. All endotracheal intubation encounters performed by the neonatal team were recorded. Results: Two hundred and fifty-eight consecutive intubation encounters in 197 patients were analyzed. One hundred and forty-eight (57.4%) intubation encounters were associated with at least one TIAE. Intubation inexperience (<10 intubation encounters) (OR = 2.15; 95% CI, 1.257-3.685) and equipment problems (OR = 3.43; 95% CI, 1.12-10.52) were predictive of TIAEs. Intubation at first attempt (OR = 0.10; 95% CI, 0.06-0.19) and videolaryngoscopy (OR = 0.47; 96% CI, 0.25-0.860) were predictive of intubation encounters without TIAEs. The first intubation attempt was commonly done by pediatric residents (67.8%). A median of two attempts were performed until successful intubation. Restricted laryngoscopic view (OR = 3.07; 95% CI, 2.08-4.53; Cormack-Lehane grade 2 vs. grade 1), intubation by pediatric residents when compared to neonatologists (OR = 1.74; 95% CI, 1.265-2.41) and support by less experienced neonatal nurses (OR = 1.60; 95% CI, 1.04-2.46) were associated with unsuccessful intubation attempts. Conclusions: In our unit, TIAEs and unsuccessful intubation attempts occurred frequently during neonatal nasotracheal intubations. To improve success rates, quality improvement und further research should target interprofessional education and training, equipment problems and videolaryngoscopy.

Chronic oxytocin-driven alternative splicing of Crfr2α induces anxiety.

The neuropeptide oxytocin (OXT) has generated considerable interest as potential treatment for psychiatric disorders, including anxiety and autism spectrum disorders. However, the behavioral and molecular consequences associated with chronic OXT treatment and chronic receptor (OXTR) activation have scarcely been studied, despite the potential therapeutic long-term use of intranasal OXT. Here, we reveal that chronic OXT treatment over two weeks increased anxiety-like behavior in rats, with higher sensitivity in females, contrasting the well-known anxiolytic effect of acute OXT. The increase in anxiety was transient and waned 5 days after the infusion has ended. The behavioral effects of chronic OXT were paralleled by activation of an intracellular signaling pathway, which ultimately led to alternative splicing of hypothalamic corticotropin-releasing factor receptor 2α (Crfr2α), an important modulator of anxiety. In detail, chronic OXT shifted the splicing ratio from the anxiolytic membrane-bound (mCRFR2α) form of CRFR2α towards the soluble CRFR2α (sCRFR2α) form. Experimental induction of alternative splicing mimicked the anxiogenic effects of chronic OXT, while sCRFR2α-knock down reduced anxiety-related behavior of male rats. Furthermore, chronic OXT treatment triggered the release of sCRFR2α into the cerebrospinal fluid with sCRFR2α levels positively correlating with anxiety-like behavior. In summary, we revealed that the shifted splicing ratio towards expression of the anxiogenic sCRFR2α underlies the adverse effects of chronic OXT treatment on anxiety.

Microleakage of pit and fissure sealings placed after enamel conditioning with phosphoric acid or with self-etching primers/adhesives.

BACKGROUND: It is still not fully understood what pretreatment is best for achieving maximum tightness for pit and fissure sealings (PFS). AIM: This study investigated microleakage of PFS placed after etching with phosphoric acid or after the application of self-etching primers/adhesives (SEPA). DESIGN: 131 third molars were assigned to ten groups. In Hel-P, Helioseal® was applied after phosphoric acid etching. In the other groups, SEPA were used (Dyr-AP: Adper™ Prompt™ L-Pop™, Dyract® Seal; Bea: BeautiSealant Primer and Paste; Hel-Exp: Experimental primer, Helioseal®; Hel-Cl: Clearfil™ SE Bond1 , Helioseal®). Specimens were stored in distilled water at 37°C (28 days), followed by 3500 thermocycles and staining with 5% methylene blue (M) or 5% silver nitrate (S). After methylene blue staining and sectioning, microleakage was assessed light microscopically. During silver nitrate staining, specimens were dissolved by 32% HCl and remaining PFS were evaluated under a SEM. RESULTS: Tightness, percentage of penetrated area, and maximum dye penetration were best for Hel-P and Hel-Cl (p < 0.05). CONCLUSIONS: Phosphoric acid etching of enamel and Clearfil™ SE Bond resulted in the best sealing quality. Methylene blue staining allowed the evaluation of more criteria (fissure shape, voids, sealant penetration depth) compared to silver nitrate.

Class II resin composite restorations-tunnel vs. box-only in vitro and in vivo.

PURPOSE: In a combined in vitro/in vivo approach, tunnel vs. box-only resin composite restorations should be evaluated using thermomechanical loading (TML) in vitro and a restrospective clinical trial in vivo. MATERIALS AND METHODS: For the in vitro part, box-only and tunnel cavities were prepared in 32 extracted human third molars under simulated intraoral conditions in a phantom head. Specimens were randomly assigned to four groups (n = 8; 16 box-only/16 tunnel) and received bonded resin composite restorations with Amelogen Plus (box A/tunnel A) or lining with Ultraseal and Amelogen plus (box B/tunnel B) both bonded using PQ1 (all Ultradent). Specimens were subjected to a standardized aging protocol, 1-year water storage (WS) followed by TML (100,000 × 50 N; 2500 × + 5/+ 55 °C). Initially and after aging, marginal qualities were evaluated using replicas at × 200 magnification (SEM). For the corresponding in vivo observational study, 229 patients received 673 proximal resin composite restorations. From 371 tunnel restorations, 205 cavities were filled without flowable lining (tunnel A), and 166 tunnels were restored using UltraSeal as lining (tunnel B). A total of 302 teeth received conventional box-only fillings. Restorations were examined according to modified USPHS criteria during routine recalls up to 5 years of clinical service. RESULTS: In vitro, all initial results showed 100% gap-free margins when a flowable lining was used. Tunnels without lining exhibited some proximal shortcomings already before TML and even more pronounced after TML (p < 0.05). After TML, percentages of gap-free margins dropped to 87-90% in enamel with lining and 70-79% without lining (p < 0.05). In vivo, annual failure rates for box-only were 2.2%, for tunnel A 6.1%, and for tunnel B 1.8%, respectively (p < 0.05). Tunnels had significantly more sufficient proximal contact points than box-only restorations (p < 0.05). Flowable lining was highly beneficial for clinical outcome of tunnel-restorations (p < 0.05). CONCLUSIONS: With a flowable lining, tunnel restorations proved to be a good alternative to box-only resin composite restorations. CLINICAL RELEVANCE: Class II tunnel restorations showed to be a viable alternative for box-only restorations, however, only when flowable resin composite was used as adaptation promotor for areas being difficult to access.