Diffuse descending necrotizing mediastinitis: surgical therapy and outcome in a single-centre series

OBJECTIVES Descending necrotizing mediastinitis (DNM) is a rare but rapidly progressing disease with a potentially fatal outcome, originating from odontogenical or cervical infections. The aim of this article was to give an up-to-date overview on this still underestimated disease, to draw the clinician's attention and particularly to highlight the need for rapid diagnosis and adequate surgical treatment. METHODS We present a retrospective analysis of 17 patients diagnosed and treated for advanced DNM between 1999 and 2011 in a tertiary referral medical centre. Hence, this is one of the largest single-centre studies in recent years concerning the diffuse form (i.e. extending into the lower mediastinum) of DNM. Subsequently, we analysed and compared the international literature with our data, with the focus on surgical management and outcome. RESULTS In our series of 17 adult patients, 16 were surgically treated by median sternotomy (n=8) or the clamshell (n=8) approach for diffuse DNM. One patient, referred with septic shock, died 2 days after surgery. The median interval from diagnosis of DNM by cervicothoracic computed tomography scan and thoracic surgery was 6h (range 1-24h) in all but the one patient with fatal outcome (48h). Concomitant cervicotomy was performed in 11 patients (65%) and tracheotomy in 9 (53%). The median duration of hospitalization was 16 days (range 4-50 days), including an intensive care unit stay of 4 days (range 1-50 days). CONCLUSIONS For DNM limited to the upper part of the mediastinum, which applies to the majority of cases, a transcervical approach and drainage may be sufficient. In advanced disease, extending below the tracheal carina, an immediate and more aggressive surgical approach is required to combat a much higher morbidity and mortality in this subset of patients. A timely situational approach via median sternotomy or a clamshell incision allowed us to maintain a very low morbidity, mortality and rate of reoperations, without major complications due to the surgical approach itsel

Robotic vs. Transsternal Thymectomy: A Single Center Experience over 10 Years.

INTRODUCTION Thymomas are the most common tumors of the mediastinum. Traditionally, thymectomies have been performed through a transsternal (TS) approach. With the development of robot-assisted thoracic surgery (RATS), a promising, minimally invasive, alternative surgical technique for performing a thymectomy has been developed. In the current paper, the oncological and surgical outcomes of the TS vs. RATS thymectomies are discussed. METHODS For the RATS thymectomy, two 8 mm working ports and one 12 mm camera port were used. In the transsternal approach, we performed a median sternotomy and resected the thymic tissue completely, in some cases en bloc with part of the lung and/or, more frequently, a partial pericardiectomy with consequent reconstruction using a bovine pericardial patch. The decisions for using the TS vs. RATS methods were mainly based on the suspected tumor invasion of the surrounding structures on the preoperative CT scan and tumor size. RESULTS Between January 2010 and November 2020, 149 patients were submitted for an anterior mediastinal tumor resection at our institution. A total of 104 patients met the inclusion criteria. One procedure was performed through a hemi-clamshell incision. A total of 81 (78%) patients underwent RATS procedures, and 22 (21.1%) patients were treated using a transsternal (TS) tumor resection. Thymoma was diagnosed in 53 (51%) cases. In the RATS group, the median LOS was 3.2 ± 2.8 days and the median tumor size was 4.4 ± 2.37 cm compared to the TS group, which had a median LOS of 9 ± 7.3 days and a median tumor size of 10.4 ± 5.3 cm. Both differences were statistically significant (p < 0.001). Complete resection was achieved in all patients. CONCLUSION While larger and infiltrating tumors (i.e., thymic carcinomas) were usually resected via a sternotomy, the RATS procedure is a good alternative for the resection of thymomas of up to 9.5 cm, and the thymectomy is a strong approach for myasthenia gravis. The oncological outcomes and survival rates were not influenced by the chosen approach

Thoracic Outlet Syndrome: Single Center Experience on Robotic Assisted First Rib Resection and Literature Review.

Background Thoracic outlet syndrome (TOS) is a pathological condition caused by a narrowing between the clavicle and first rib leading to a compression of the neurovascular bundle to the upper extremity. The incidence of TOS is probably nowadays underestimated because the diagnosis could be very challenging without a thorough clinical examination along with appropriate clinical testing. Beside traditional supra-, infraclavicular or transaxillary approaches, the robotic assisted first rib resection has been gaining importance in the last few years. Methods We conducted a retrospective cohort analysis of all patients who underwent robotic assisted first rib resection due to TOS at Lucerne Cantonal Hospital and then we performed a narrative review of the English literature using PubMed, Cochrane Database of Systematic Reviews and Scopus. Results Between June 2020 and November 2021, eleven robotic assisted first rib resections were performed due to TOS at Lucerne Cantonal Hospital. Median length of stay was 2 days (Standard Deviation: +/- 0.67 days). Median surgery time was 180 min (Standard Deviation: +/- 36.5). No intra-operative complications were reported. Conclusions Robotic assisted first rib resection could represent a safe and feasible option in expert hands for the treatment of thoracic outlet syndrome

Randomized Controlled Trial of Thresholds for Drain Removal After Anatomic Lung Resection.

BACKGROUND The criteria for chest drain removal following lung resections remain vague and rely on personal experience instead of evidence. Since pleural fluid resorption is proportional to body weight, a weight-related approach seems reasonable. We examined the feasibility of a weight-adjusted fluid output threshold concerning postoperative respiratory complications and the occurrence of symptomatic pleural effusion after chest drain removal. Our secondary objectives were the length of hospital stay and the pain levels before and after chest drain removal. METHODS Single-center randomized controlled trial including 337 patients planned for open or thoracoscopic anatomical lung resections. Patients were randomized postoperatively into two groups. The chest drain was removed in the study group according to a fluid output threshold calculated by the 5 mL x body weight (in kg) / 24 hours formula. In the control group, our previous traditional fluid threshold of 200 mL/ 24 hours was applied. RESULTS No differences were evident regarding the occurrence of pleural effusion, dyspnea at discharge and 30 days postoperatively. In the logistic regression analysis, the surgical modality was a risk factor for other complications, and age was the only variable influencing postoperative dyspnea. Time to chest drain removal was identical in both groups, and time to discharge was shorter following open surgery in the test group. CONCLUSIONS No increased postoperative complications occurred with this weight-based formula, and a trend toward earlier discharge after open surgery was observed in the test group

Targeting lactate dehydrogenase B-dependent mitochondrial metabolism affects tumor initiating cells and inhibits tumorigenesis of non-small cell lung cancer by inducing mtDNA damage.

Once considered a waste product of anaerobic cellular metabolism, lactate has been identified as a critical regulator of tumorigenesis, maintenance, and progression. The putative primary function of lactate dehydrogenase B (LDHB) is to catalyze the conversion of lactate to pyruvate; however, its role in regulating metabolism during tumorigenesis is largely unknown. To determine whether LDHB plays a pivotal role in tumorigenesis, we performed 2D and 3D in vitro experiments, utilized a conventional xenograft tumor model, and developed a novel genetically engineered mouse model (GEMM) of non-small cell lung cancer (NSCLC), in which we combined an LDHB deletion allele with an inducible model of lung adenocarcinoma driven by the concomitant loss of p53 (also known as Trp53) and expression of oncogenic KRAS (G12D) (KP). Here, we show that epithelial-like, tumor-initiating NSCLC cells feature oxidative phosphorylation (OXPHOS) phenotype that is regulated by LDHB-mediated lactate metabolism. We show that silencing of LDHB induces persistent mitochondrial DNA damage, decreases mitochondrial respiratory complex activity and OXPHOS, resulting in reduced levels of mitochondria-dependent metabolites, e.g., TCA intermediates, amino acids, and nucleotides. Inhibition of LDHB dramatically reduced the survival of tumor-initiating cells and sphere formation in vitro, which can be partially restored by nucleotide supplementation. In addition, LDHB silencing reduced tumor initiation and growth of xenograft tumors. Furthermore, we report for the first time that homozygous deletion of LDHB significantly reduced lung tumorigenesis upon the concomitant loss of Tp53 and expression of oncogenic KRAS without considerably affecting the animal's health status, thereby identifying LDHB as a potential target for NSCLC therapy. In conclusion, our study shows for the first time that LDHB is essential for the maintenance of mitochondrial metabolism, especially nucleotide metabolism, demonstrating that LDHB is crucial for the survival and proliferation of NSCLC tumor-initiating cells and tumorigenesis

Hundreds of variants clustered in genomic loci and biological pathways affect human height

Most common human traits and diseases have a polygenic pattern of inheritance: DNA sequence variants at many genetic loci influence the phenotype. Genome-wide association (GWA) studies have identified more than 600 variants associated with human traits, but these typically explain small fractions of phenotypic variation, raising questions about the use of further studies. Here, using 183,727 individuals, we show that hundreds of genetic variants, in at least 180 loci, influence adult height, a highly heritable and classic polygenic trait. The large number of loci reveals patterns with important implications for genetic studies of common human diseases and traits. First, the 180 loci are not random, but instead are enriched for genes that are connected in biological pathways (P = 0.016) and that underlie skeletal growth defects (P < 0.001). Second, the likely causal gene is often located near the most strongly associated variant: in 13 of 21 loci containing a known skeletal growth gene, that gene was closest to the associated variant. Third, at least 19 loci have multiple independently associated variants, suggesting that allelic heterogeneity is a frequent feature of polygenic traits, that comprehensive explorations of already-discovered loci should discover additional variants and that an appreciable fraction of associated loci may have been identified. Fourth, associated variants are enriched for likely functional effects on genes, being over-represented among variants that alter amino-acid structure of proteins and expression levels of nearby genes. Our data explain approximately 10% of the phenotypic variation in height, and we estimate that unidentified common variants of similar effect sizes would increase this figure to approximately 16% of phenotypic variation (approximately 20% of heritable variation). Although additional approaches are needed to dissect the genetic architecture of polygenic human traits fully, our findings indicate that GWA studies can identify large numbers of loci that implicate biologically relevant genes and pathways.

PET and MRI for the evaluation of regional myocardial perfusion and wall thickening after myocardial infarction

Deterioration of left ventricular (LV) function after myocardial infarction (MI) is a major cause of heart failure. Myocardial perfusion performance may play an important role in deterioration or improvement in LV function after MI. The aim of this study was to evaluate the myocardial perfusion reserve (MPR) and stress perfusion in deteriorating and non-deteriorating LV segments in patients after MI by PET and MRI, respectively. Regional wall thickening of 352 segments in 22 patients was assessed at 4 and 24 months after MI by cardiac MRI. PET was performed to evaluate MPR and adenosine stress N-13-ammonia perfusion 24 months after MI. Segments were divided into four groups according to deterioration or improvement in wall thickening. Normal functional segments at 4 months after MI that remained stable had a significantly higher mean MPR and mean stress perfusion PET value than deteriorated segments (p < 0.001). Furthermore, dysfunctional segments that improved had a significantly higher mean stress perfusion PET value than dysfunctional segments that remained dysfunctional (p < 0.001). This study demonstrated the additional value of myocardial perfusion assessment in relation to the functional integrity of the injured myocardium. Segmental functional LV improvement after MI was associated with better regional myocardial perfusion characteristics. Furthermore, the amount of wall thickening reduction was associated with regional myocardial perfusion abnormalities in patients after MI

The Contribution of the Pineal Gland on Daily Rhythms and Masking in Diurnal Grass Rats, Arvicanthis niloticus

Melatonin is a hormone rhythmically secreted at night by the pineal gland in vertebrates. In diurnal mammals, melatonin is present during the inactive phase of the rest/activity cycle, and in primates it directly facilitates sleep and decreases body temperature. However, the role of the pineal gland for the promotion of sleep at night has not yet been studied in non-primate diurnal mammalian species. Here, the authors directly examined the hypothesis that the pineal gland contributes to diurnality in Nile grass rats by decreasing activity and increasing sleep at night, and that this could occur via effects on circadian mechanisms or masking, or both. Removing the pineal gland had no effect on the hourly distribution of activity across a 12:12 light-dark (LD) cycle or on the patterns of sleep-like behavior at night. Masking effects of light at night on activity were also not significantly different in pinealectomized and control grass rats, as 1h pulses of light stimulated increases in activity of sham and pinealectomized animals to a similar extent. In addition, the circadian regulation of activity was unaffected by the surgical condition of the animals. Our results suggest that the pineal gland does not contribute to diurnality in the grass rat, thus highlighting the complexity of temporal niche transitions. The current data raise interesting questions about how and why genetic and neural mechanisms linking melatonin to sleep regulatory systems might vary among mammals that reached a diurnal niche via parallel and independent pathways

Response to a sexual risk reduction intervention provided in combination with hepatitis C treatment by HIV/HCV co-infected men who have sex with men: a reflexive thematic analysis.

BACKGROUND: Hepatitis C virus reinfections in HIV-positive men-who-have-sex-with-men (MSM) challenge the effectiveness of antiviral treatment. To fight this problem, an adapted sexual risk reduction intervention was implemented within a hepatitis C treatment trial. Following this, the current study had two aims and describes 1) how the program was received by participants; and 2) their responses to the program regarding sexual risk taking. Based on the participants' input, we hoped to judge the intervention's potential for scale-up. METHODS: Seventeen participants who received the sexual risk reduction intervention in addition to hepatitis C treatment were recruited for semi-structured interviews six to 12 months post-intervention. We evaluated the responses via reflexive thematic analysis and applied the concept of sense-making. RESULTS: Giving hepatitis C a place and living without it again illustrates how participants received the program and how their experiences were altered by the impact of sense-making. Based on their responses, we allocated participants to three groups: 1. Avoid risks: get rid of hepatitis C for life. For these men, hepatitis C remained a life-threatening disease: they actively modified their risk behavior and felt supported by the intervention in maintaining their behavioral changes. 2. Minimize risks: live as long as possible without hepatitis C. In contrast to group 1, these men saw hepatitis C as a manageable disease. The intervention facilitated reflection on risks and how to develop behavioral changes that suited them individually. 3. Accept risks; live with the risk of hepatitis C. These men perceived behavioral changes as much more difficult than "easy" medical treatment. They expected to either undergo repeated rounds of treatment or stay HCV re-infected. CONCLUSION: These results illustrate the diversity of men's responses and their decisions regarding sexual risk behavior after participating in a combination of antiviral treatment and a sexual risk reduction intervention. Two major aspects were identified: 1) Teachable moments, particularly at the time of diagnosis/treatment, could offer an opportunity to develop openness for behavioral change; 2) adapting sexual risk reduction interventions to sense-making patterns could help to improve its effectiveness. Support for reducing infection risk and raising awareness of preventative measures are additional benefits. TRIAL REGISTRATION: Clinical Trial Number: NCT02785666 , 30.05.2016