Non-coding RNA's prevalence as biomarkers for prognostic, diagnostic, and clinical utility in breast cancer.

Noncoding RNAs (ncRNAs), which make up a significant portion of the mammalian transcriptome and plays crucial regulatory roles in expression of genes and other biological processes, have recently been found. The most extensively researched of the sncRNAs, microRNAs (miRNAs), have been characterized in terms of their synthesis, roles, and significance in the tumor development. Its crucial function in the stem cell regulation, another class of sncRNAs known as aspirRNAs, has attracted attention in cancer research. The investigations have shown that long non-coding RNAs have a crucial role in controlling developmental stages, such as mammary gland development. Additionally, it has been discovered that lncRNA dysregulation precedes the development of several malignancies, including breast cancer. The functions of sncRNAs (including miRNAs and piRNAs) and lncRNAs in the onset and development of the breast cancer are described in this study. Additionally, future perspectives of various ncRNA-based diagnostic, prognostic, and therapeutic approaches also discussed.

Complement Inhibitors in the Management of Complement-Mediated Hemolytic Uremic Syndrome and Paroxysmal Nocturnal Hemoglobinuria.

BACKGROUND: Complement-mediated HUS (CM-HUS) and paroxysmal nocturnal hemoglobinuria (PNH) are rare hematologic disorders that cause dysregulation and hyperactivation of the complement system. Historically, treatment of CM-HUS involved plasma exchange (PLEX), often with limited benefit and variable tolerance. Conversely, PNH was treated with supportive care or hemopoietic stem cell transplant. Within the last decade, monoclonal antibody therapies that block terminal complement pathway activation, have emerged as less invasive and more efficacious options for management of both disorders. This manuscript seeks to discuss a relevant clinical case of CM-HUS and the evolving landscape of complement inhibitor therapies for CM-HUS and PNH. AREAS OF UNCERTAINTY: Eculizumab, the first humanized anti-C5 monoclonal antibody, has been the standard of care in treating CM-HUS and PNH for over a decade. Although eculizumab has remained an effective agent, the variability in ease and frequency of administration has remained an obstacle for patients. The development of novel complement inhibitor therapies with longer half-lives, has allowed for changes in frequency and route of administration, thus improving patient QOL. However, there are limited prospective clinical trial data given disease rarity, and limited information on variable infusion frequency and length of treatment. THERAPEUTIC ADVANCES: Recently, there has been a push to formulate complement inhibitors that improve QOL while maintaining efficacy. Ravulizumab, a derivative of eculizumab, was developed to allow for less frequent administration, while remaining efficacious. In addition, the novel oral and subcutaneous therapies, danicopan and crovalimab, respectively, along with pegcetacoplan are currently undergoing active clinical trials, and poised to further reduce treatment burden. CONCLUSION: Complement inhibitor therapies have changed the treatment landscape for CM-HUS and PNH. With a significant emphasis on patient QOL, novel therapies continue to emerge and require an in-depth review of their appropriate use and efficacy in these rare disorders. CLINICAL CASE: A 47-year-old woman with hypertension and hyperlipidemia presented with shortness of breath and was found to have hypertensive emergency in the setting of acute renal failure. Her serum creatinine was 13.9 mg/dL; elevated from 1.43 mg/dL 2 years before. The differential diagnosis for her acute kidney injury (AKI) included infectious, autoimmune, and hematologic processes. Infectious work-up was negative. ADAMTS13 activity level was not low at 72.9%, ruling out thrombotic thrombocytopenic purpura (TTP). Patient underwent a renal biopsy, which revealed acute on chronic thrombotic microangiopathy (TMA). A trial of eculizumab was initiated with concurrent hemodialysis. The diagnosis of CM-HUS was later confirmed by a heterozygous mutation in complement factor I (CFI), resulting in increased membrane attack complex (MAC) cascade activation. The patient was maintained on biweekly eculizumab and was eventually transitioned to ravulizumab infusions as an outpatient. Her renal failure did not recover, and the patient remains on hemodialysis while awaiting kidney transplantation.

Immunological and inflammatory effects of infectious diseases in circadian rhythm disruption and future therapeutic directions.

BACKGROUND: Circadian rhythm is characterised by daily variations in biological activity to align with the light and dark cycle. These diurnal variations, in turn, influence physiological functions such as blood pressure, temperature, and sleep-wake cycle. Though it is well established that the circadian pathway is linked to pro-inflammatory responses and circulating immune cells, its association with infectious diseases is widely unknown. OBJECTIVE: This comprehensive review aims to describe the association between circadian rhythm and host immune response to various kinds of infection. METHODS: We conducted a literature search in databases Pubmed/Medline and Science direct. Our paper includes a comprehensive analysis of findings from articles in English which was related to our hypothesis. FINDINGS: Molecular clocks determine circadian rhythm disruption in response to infection, influencing the host's response toward infection. Moreover, there is a complex interplay with intrinsic oscillators of pathogens and the influence of specific infectious processes on the CLOCK: BMAL1 pathway. Such mechanisms vary for bacterial and viral infections, both well studied in the literature. However, less is known about the association of parasitic infections and fungal pathogens with circadian rhythm modulation. CONCLUSION: It is shown that bidirectional relationships exist between circadian rhythm disruption and infectious process, which contains interplay between the host's and pathogens' circadian oscillator, immune response, and the influence of specific infectious. Further studies exploring the modulations of circadian rhythm and immunity can offer novel explanations of different susceptibilities to infection and can lead to therapeutic avenues in circadian immune modulation of infectious diseases.

When Will Fondaparinux Induce Thrombocytopenia?

The pentasaccharide Fondaparinux, a synthetic selective factor Xa inhibitor, is one of the safest anticoagulants in the heparin family that is recommended as an alternative drug for patients with hypersensitivity to other drugs such as heparin-induced thrombocytopenia (HIT). However, some observations of Fondaparinux-induced thrombocytopenia (FIT) have been reported while others claimed that FIT does not occur in patients with fondaparinux therapy, indicating that the mechanism of FIT remains controversial. Here, we utilized different methodologies including dynamic light scattering, immunosorbent and platelet aggregation assays, confocal laser scanning microscopy, and flow cytometry to gain insights into FIT. We found that at a certain concentration, Fondaparinux formed sufficient large and stable complexes with PF4 that facilitated binding of the HIT-like monoclonal KKO antibody and enhanced platelet aggregation and activation. We proposed a model to describe the role of Fondaparinux concentration in the formation of complexes with platelet factor 4 and how it promotes the binding of KKO. Our results clarify controversial observations of FIT in patients as each contains a dissimilar PF4:Fondaparinux concentration ratio.

High-frequency Contactless Sensor for the Detection of Heparin-Induced Thrombocytopenia Antibodies via Platelet Aggregation.

Heparin-induced thrombocytopenia (HIT), a severe autoimmune disorder, occurs in patients undergoing heparin therapy. The presence of platelet-activating antibodies against platelet factor 4/Heparin in the blood confirms patients suffering from HIT. The most widely used methods for HIT diagnosis are immunoassays but the results only suit to rule out HIT as the assays provide only around 50% specificity. To confirm HIT, samples with positive results in immunoassays are retested in functional assays (>98% specificity) that track platelet-activating antibodies via platelet aggregation. However, the protocols in functional assays are either time-consuming (due to the requirement of the detection of serotonin release) or require highly trained staff for the visualization of platelets. Here, we applied a cheap and easy-to-use contactless sensor, which employs high-frequency microwaves to detect the changes in the resonant frequency caused by platelet aggregation/activation. Analysis of change in conductivity and permittivity allowed us to distinguish between HIT-like (KKO) and non-HIT-like (RTO) antibodies. KKO caused a stronger reduction of conductivity of platelet samples than RTO. Our results imply that the high-frequency contactless sensor can be a promising approach for the development of a better and easier method for the detection of HIT.

Tetraspanin CD82 Organizes Dectin-1 into Signaling Domains to Mediate Cellular Responses to Candida albicans.

Tetraspanins are a family of proteins possessing four transmembrane domains that help in lateral organization of plasma membrane proteins. These proteins interact with each other as well as other receptors and signaling proteins, resulting in functional complexes called "tetraspanin microdomains." Tetraspanins, including CD82, play an essential role in the pathogenesis of fungal infections. Dectin-1, a receptor for the fungal cell wall carbohydrate ß-1,3-glucan, is vital to host defense against fungal infections. The current study identifies a novel association between tetraspanin CD82 and Dectin-1 on the plasma membrane of Candida albicans-containing phagosomes independent of phagocytic ability. Deletion of CD82 in mice resulted in diminished fungicidal activity, increased C. albicans viability within macrophages, and decreased cytokine production (TNF-α, IL-1ß) at both mRNA and protein level in macrophages. Additionally, CD82 organized Dectin-1 clustering in the phagocytic cup. Deletion of CD82 modulates Dectin-1 signaling, resulting in a reduction of Src and Syk phosphorylation and reactive oxygen species production. CD82 knockout mice were more susceptible to C. albicans as compared with wild-type mice. Furthermore, patient C. albicans-induced cytokine production was influenced by two human CD82 single nucleotide polymorphisms, whereas an additional CD82 single nucleotide polymorphism increased the risk for candidemia independent of cytokine production. Together, these data demonstrate that CD82 organizes the proper assembly of Dectin-1 signaling machinery in response to C. albicans.

Evaluation of hematological parameters as an indicator of disease severity in Covid-19 patients: Pakistan's experience.

BACKGROUND: The severity of COVID-19 could be evaluated by examining several blood parameters mainly white blood cell (WBC) count, granulocytes, platelet, and novel hemocytometric markers neutrophils to lymphocyte ratio (NLR), platelet-to-lymphocyte (PLR), and lymphocyte to monocyte ratio (LMR). The current study was conducted to investigate alteration in blood parameters and their association with the severity and mortality of COVID-19 patients. METHODOLOGY: An observational cross-sectional study was conducted retrospectively, a total of 101 COVID-19 positive patients were examined: 52 were mild, 24 were moderate, 09 were severe, and 16 were critically diseased patients. We also recorded 16 deaths associated with the critical group. The overall mean age observed in our study was 48.94 years, where the mean age for critical individuals was 62.12 ± 14.35 years. RESULTS: A significant association between the disease severity and elevation in blood parameters were observed. The WBC's and granulocyte count were significantly increased (p value <0.001) while the mean platelet count (165.0 × 109 /L) and red blood cell volume distribution width (RDW) were decreased in the critical group (57.86%) compared to mild group's patients (177.3%) (p = 0.83). The lymphocytes count was decreased in critical patients (1.40 × 109 /L) compared to mild patients (1.92 × 109 /L) (p = 0.28). A significant association was observed in platelet-lymphocyte ratio (p < 0.001), Neutrophil-Lymphocyte ratio (p = <0.001), and Lymphocyte-Monocyte ratio (0.011). CONCLUSION: These blood parameters could be used as a suitable biomarker for the prognosis and severity of COVID-19. Evaluating novel hemograms NLR, PLR, and LMR can aid clinicians to identify potentially severe cases at early stages, initiate effective management in time, and conduct early triage which may reduce the overall mortality of COVID-19 patients.

CD82 controls CpG-dependent TLR9 signaling.

The tetraspanin CD82 is a potent suppressor of tumor metastasis and regulates several processes including signal transduction, cell adhesion, motility, and aggregation. However, the mechanisms by which CD82 participates in innate immunity are unknown. We report that CD82 is a key regulator of TLR9 trafficking and signaling. TLR9 recognizes unmethylated cytosine-phosphate-guanine (CpG) motifs present in viral, bacterial, and fungal DNA. We demonstrate that TLR9 and CD82 associate in macrophages, which occurs in the endoplasmic reticulum (ER) and post-ER. Moreover, CD82 is essential for TLR9-dependent myddosome formation in response to CpG stimulation. Finally, CD82 modulates TLR9-dependent NF-κB nuclear translocation, which is critical for inflammatory cytokine production. To our knowledge, this is the first time a tetraspanin has been implicated as a key regulator of TLR signaling. Collectively, our study demonstrates that CD82 is a specific regulator of TLR9 signaling, which may be critical in cancer immunotherapy approaches and coordinating the innate immune response to pathogens.-Khan, N. S., Lukason, D. P., Feliu, M., Ward, R. A., Lord, A. K., Reedy, J. L., Ramirez-Ortiz, Z. G., Tam, J. M., Kasperkovitz, P. V., Negoro, P. E., Vyas, T. D., Xu, S., Brinkmann, M. M., Acharaya, M., Artavanis-Tsakonas, K., Frickel, E.-M., Becker, C. E., Dagher, Z., Kim, Y.-M., Latz, E., Ploegh, H. L., Mansour, M. K., Miranti, C. K., Levitz, S. M., Vyas, J. M. CD82 controls CpG-dependent TLR9 signaling.

Biochemical spectrum of parathyroid disorders diagnosed at a tertiary care setting.

OBJECTIVE: To determine the clinical and biochemical pattern of parathyroid disorders in a tertiary care setting.. METHODS: The cross-sectional study was conducted at the Armed Forces Institute of Pathology, Rawalpindi, Pakistan, from September 2017 to February 2018, and comprised patients with suspected parathyroid disorders. A panel of biochemical tests were used for diagnosis of parathyroid disorders, which included parathyroid hormone levels, total calcium, ionized calcium, inorganic phosphorus, alkaline phosphatase, magnesium, total vitamin D and urinary calcium-to-creatinine ratio. SPSS 24 was used for data analysis. RESULTS: Of the 384 subjects, 248(65%) were male and 136(35%) were female. Overall mean age was 48±19years. Of the total, 302(786%) had parathyroid issues, with 244(81%) having secondary hyperparathyroidism. Mean serum total calcium, phosphorus, ionized calcium, magnesium and total vitamin D were 8.98±1.52 mg/dl, 4.0±1.30 mg/dl, 4.65±0.52 mg/dl, 2.11±0.27 mg/dl and 20.5±8.52 ngml respectively. Of the patients diagnosed with secondary hyperparathyroidism, 72.2% patients had chronic kidney disease and 20.2% had isolated vitamin D deficiency. CONCLUSIONS: Parathyroid disorders had significant impact on bone health. Moreover, secondary hyperparathyroidism was seen to be emerging as a major endocrine problem, especially in chronic kidney disease patients and vitamin D-deficient individuals.

Dectin-1 Controls TLR9 Trafficking to Phagosomes Containing ß-1,3 Glucan.

Dectin-1 and TLR9 play distinct roles in the recognition and induction of innate immune responses to Aspergillus fumigatus and Candida albicans. Dectin-1 is a receptor for the major fungal cell wall carbohydrate ß-1,3 glucan that induces inflammatory cytokines and controls phagosomal maturation through spleen tyrosine kinase activation. TLR9 is an endosomal TLR that also modulates the inflammatory cytokine response to fungal pathogens. In this study, we demonstrate that ß-1,3 glucan beads are sufficient to induce dynamic redistribution and accumulation of cleaved TLR9 to phagosomes. Trafficking of TLR9 to A. fumigatus and C. albicans phagosomes requires Dectin-1 recognition. Inhibition of phagosomal acidification blocks TLR9 accumulation on phagosomes containing ß-1,3 glucan beads. Dectin-1-mediated spleen tyrosine kinase activation is required for TLR9 trafficking to ß-1,3 glucan-, A. fumigatus-, and C. albicans-containing phagosomes. In addition, Dectin-1 regulates TLR9-dependent gene expression. Collectively, our study demonstrates that recognition of ß-1,3 glucan by Dectin-1 triggers TLR9 trafficking to ß-1,3 glucan-containing phagosomes, which may be critical in coordinating innate antifungal defense.

Real-Time Analysis of a Sensor's Data for Automated Decision Making in an IoT-Based Smart Home.

IoT devices frequently generate large volumes of streaming data and in order to take advantage of this data, their temporal patterns must be learned and identified. Streaming data analysis has become popular after being successfully used in many applications including forecasting electricity load, stock market prices, weather conditions, etc. Artificial Neural Networks (ANNs) have been successfully utilized in understanding the embedded interesting patterns/behaviors in the data and forecasting the future values based on it. One such pattern is modelled and learned in the present study to identify the occurrence of a specific pattern in a Water Management System (WMS). This prediction aids in making an automatic decision support system, to switch OFF a hydraulic suction pump at the appropriate time. Three types of ANN, namely Multi-Input Multi-Output (MIMO), Multi-Input Single-Output (MISO), and Recurrent Neural Network (RNN) have been compared, for multi-step-ahead forecasting, on a sensor's streaming data. Experiments have shown that RNN has the best performance among three models and based on its prediction, a system can be implemented to make the best decision with 86% accuracy.

The Carbohydrate Lectin Receptor Dectin-1 Mediates the Immune Response to Exserohilum rostratum.

Dematiaceous molds are found ubiquitously in the environment and cause a wide spectrum of human disease, including infections associated with high rates of mortality. Despite this, the mechanism of the innate immune response has been less well studied, although it is key in the clearance of fungal pathogens. Here, we focus on Exserohilum rostratum, a dematiaceous mold that caused 753 infections during a multistate outbreak due to injection of contaminated methylprednisolone. We show that macrophages are incapable of phagocytosing Exserohilum Despite a lack of phagocytosis, macrophage production of tumor necrosis factor alpha is triggered by hyphae but not spores and depends upon Dectin-1, a C-type lectin receptor. Dectin-1 is specifically recruited to the macrophage-hyphal interface but not the macrophage-spore interface due to differences in carbohydrate antigen expression between these two fungal forms. Corticosteroid and antifungal therapy perturb this response, resulting in decreased cytokine production. In vivo soft tissue infection in wild-type mice demonstrated that Exserohilum provokes robust neutrophilic and granulomatous inflammation capable of thwarting fungal growth. However, coadministration of methylprednisolone acetate results in robust hyphal tissue invasion and a significant reduction in immune cell recruitment. Our results suggest that Dectin-1 is crucial for macrophage recognition and the macrophage response to Exserohilum and that corticosteroids potently attenuate the immune response to this pathogen.

Eps15 homology domain containing protein of Plasmodium falciparum (PfEHD) associates with endocytosis and vesicular trafficking towards neutral lipid storage site.

The human malaria parasite, Plasmodium falciparum, takes up numerous host cytosolic components and exogenous nutrients through endocytosis during the intra-erythrocytic stages. Eps15 homology domain-containing proteins (EHDs) are conserved NTPases, which are implicated in membrane remodeling and regulation of specific endocytic transport steps in eukaryotic cells. In the present study, we have characterized the dynamin-like C-terminal Eps15 homology domain containing protein of P. falciparum (PfEHD). Using a GFP-targeting approach, we studied localization and trafficking of PfEHD in the parasite. The PfEHD-GFP fusion protein was found to be a membrane bound protein that associates with vesicular network in the parasite. Time-lapse microscopy studies showed that these vesicles originate at parasite plasma membrane, migrate through the parasite cytosol and culminate into a large multi-vesicular like structure near the food-vacuole. Co-staining of food vacuole membrane showed that the multi-vesicular structure is juxtaposed but outside the food vacuole. Labeling of parasites with neutral lipid specific dye, Nile Red, showed that this large structure is neutral lipid storage site in the parasites. Proteomic analysis identified endocytosis modulators as PfEHD associated proteins in the parasites. Treatment of parasites with endocytosis inhibitors obstructed the development of PfEHD-labeled vesicles and blocked their targeting to the lipid storage site. Overall, our data suggests that the PfEHD is involved in endocytosis and plays a role in the generation of endocytic vesicles at the parasite plasma membrane, that are subsequently targeted to the neutral lipid generation/storage site localized near the food vacuole.

Structured performance monitoring of TB-care at facility, district and province levels - Pakistan experience.

OBJECTIVE: To develop and evaluate a more structured process for effective tuberculosis control monitoring. METHODS: The quasi-experimental exploratory study was conducted from April 2007 to January 2008 in the Punjab province of Pakistan. Eight intervention districts were compared with eight control districts. Intervention consisted of managers using performance monitoring guidelines and tools for monitoring meetings at the facility and district levels. Proportion of tuberculosis suspects among outpatients, registered confirmed cases and patients' default rate were monitored. Semi-structured interviews were done to assess the experience of the participants. RESULTS: The proportion of TB suspects among outpatient attendees was significantly higher in the intervention districts (95% confidence interval 1.6-1.8%). The pre-registration default also showed difference (p=0.07). The case finding during 9 months of the intervention showed 96.3% increase compared to the 9 months of the preceding year. CONCLUSIONS: The new process was effective in improving tuberculosis case finding. The process may be used to improve tuberculosis monitoring systems and other such healthcare services.

Dectin-1-dependent LC3 recruitment to phagosomes enhances fungicidal activity in macrophages.

Autophagy has been postulated to play role in mammalian host defense against fungal pathogens, although the molecular details remain unclear. Here, we show that primary macrophages deficient in the autophagic factor LC3 demonstrate diminished fungicidal activity but increased cytokine production in response to Candida albicans stimulation. LC3 recruitment to fungal phagosomes requires activation of the fungal pattern receptor dectin-1. LC3 recruitment to the phagosome also requires Syk signaling but is independent of all activity by Toll-like receptors and does not require the presence of the adaptor protein Card9. We further demonstrate that reactive oxygen species generation by NADPH oxidase is required for LC3 recruitment to the fungal phagosome. These observations directly link LC3 to the inflammatory pathway against C. albicans in macrophages.

Dectin-1 activation controls maturation of ß-1,3-glucan-containing phagosomes.

Elimination of fungal pathogens by phagocytes requires phagosome maturation, a process that involves the recruitment and fusion of intracellular proteins. The role of Dectin-1, a ß-1,3-glucan receptor, critical for fungal recognition and triggering of Th17 responses, to phagosomal maturation has not been defined. We show that GFP-Dectin-1 translocates to the fungal phagosome, but its signal decays after 2 h. Inhibition of acidification results in retention of GFP-Dectin-1 to phagosome membranes highlighting the requirement for an acidic pH. Following ß-1,3-glucan recognition, GFP-Dectin-1 undergoes tyrosine phosphorylation by Src kinases with subsequent Syk activation. Our results demonstrate that Syk is activated independently of intraphagosomal pH. Inhibition of Src or Syk results in prolonged retention of GFP-Dectin-1 to the phagosome signifying a link between Syk and intraphagosomal pH. ß-1,3-glucan phagosomes expressing a signaling incompetent Dectin-1 failed to mature as demonstrated by prolonged Dectin-1 retention, presence of Rab5B, failure to acquire LAMP-1 and inability to acidify. Phagosomes containing Candida albicans also require Dectin-1-dependent Syk activation for phagosomal maturation. Taken together, these results support a model where Dectin-1 not only controls internalization of ß-1,3-glucan containing cargo and triggers proinflammatory cytokines, but also acts as a master regulator for subsequent phagolysosomal maturation through Syk activation.

Macroalgae farming for sustainable future: Navigating opportunities and driving innovation.

Seaweed cultivation has garnered significant interest, driven by its wide range of biomass benefits. However, comprehensive assessments from various perspectives are imperative to ensure the sustainable cultivation of seaweed. Biotic and Abiotic factors can significantly impact seaweed yield in complex commercial farming. Biotic factors include bacteria, fungi, viruses, and other algae, while abiotic factors include environmental conditions such as temperature, salinity, light intensity, and nutrient availability. Additionally, the susceptibility of seaweeds to pests and diseases further compounds the issue, leading to potential crop losses. This study endeavours to shed light on the immense potential of macroalgae cultivation and underscores the pressing need for scientific advancements in this field. The comprehensive review clearly explains the latest developments in seaweed cultivation and highlights significant advances from diverse seaweed research. Moreover, it provides insightful glimpses into possible future developments that could shape the trajectory of this promising industry.

A Long-term Evaluation of Acellular Dermal Matrix for Immediate Implant-based Breast Reconstruction following Risk-reducing Mastectomy.

Background: Acellular dermal matrices (ADMs) are sometimes used in implant-based breast reconstructions (IBR), but long-term ADM-related evaluations are scarce. In this study, we evaluated early and late complications and patient-related outcomes (PROs) over an 8-year postoperative period in women who had undergone immediate IBR following risk-reducing mastectomy with bovine ADM (SurgiMend). Methods: This prospective observational single-center analysis involved 34 women at high risk for breast carcinoma. Complications were prospectively recorded during the first year, followed by 4 years of postoperative retrospective chart reviews. Long-term evaluations were done using a questionnaire. Preoperative, 1 year, and 5- to 8-year postoperative PRO assessments were obtained based on results from the BREAST-Q questionnaire. Results: In 56 breasts, complications after a mean of 12.4 months follow-up included implant loss (7.1%), implant change (1.8%), hematoma (7.1%), breast redness (41.1%), and seroma (8.9%). Most breasts (80.3%) were graded Baker I/II, which indicated a low capsular contracture incidence. After a mean of 6.9 years, the total implant explantation rate was 33.9%, and the revision surgery rate was 21.4%. Two cases of breast cancer were reported during the long-term evaluation. BREAST-Q results indicated significantly decreased satisfaction with outcome (P = 0.024). A positive trend regarding psychosocial well-being and declining trend regarding satisfaction with both breast physical- and sexual well-being parameters were reported. Conclusions: The observed complication rates agree with previous findings concerning ADM-assisted IBR. A high demand for revision surgery exists, and PROs remain relatively stable over time.