Tailored management of stage IIIa non-small-cell lung cancer in the era of the 8th edition of the TNM classification for lung cancer.

Stage IIIA is a very heterogeneous group encompassing locally advanced disease with T3 and T4 tumors without any nodal involvement and very small T1a primary tumors with unilateral mediastinal lymphatic disease. Tailored management defines interdisciplinary management requiring board decisions, which can sometimes be difficult particularly in stage IIIa non-small-cell lung cancer (NSCLC). Lobectomy still is standard of care even for stage I NSCLC, which increasingly is implemented using minimally invasive surgical technique. On the other hand even locally extended tumors are today safely resected with low morbidity and mortality. According to the 2015 guidelines of the European Society of Thoracic Surgeons any kind of anatomical lung resection for lung cancer with curative intent has to be accompanied by formal mediastinal lymph node dissection. The transcervical route for complete bilateral mediastinal lymphadenectomy offers improved completeness of resection without the need for single lung ventilation and ideally supports the concept of minimally invasive surgery.

Prognostic factors of recurrence and disease-free survival in radically resected pulmonary carcinoids: a real-world analysis.

Background: Pulmonary carcinoids (PCs) are rare neuroendocrine lung tumors which may recur, thus worsening their otherwise favorable overall prognosis. Aiming to identify patients at risk for recurrence, we examined parameters affecting disease-free survival (DFS). Methods: A retrospective single-center analysis of 82 consecutive patients undergoing curative intent resection for primary PC tumors between 2010 and 2019 was carried out. Kaplan-Meier method was utilized for survival analysis. Independent prognostic factors were determined using multivariable Cox and logistic regression. Results: During the observation period 82 patients, 48 females (58.5%) and 34 males (41.5%) were operated, representing 84 cases of PCs, 56 typical (TCs) (66.7%) and 28 atypical (ACs) (33.3%) carcinoids. Five-year overall survival was 87.5% and 84.7%, 5-year DFS 97.5% and 74.9% (P=0.012) for TCs and ACs, respectively. Recurrences occurred in one patient (1.8%) with TCs and five patients (17.9%) with ACs (P=0.014). Using multivariable Cox regression, tumor size (cm) remained as an independent prognostic factor for reduced DFS (P=0.018). In logistic regression, nodal involvement (P=0.043) and tumor size (cm) (P=0.023) were independently associated with higher risk of recurrence. Age, sex, smoking, location, and Ki-67 index were not independently associated with recurrence or DFS. Conclusions: Recurrence in PCs after complete resection is relatively rare. However, DFS is reduced in ACs compared to TCs. Tumor size (cm) and nodal involvement appear as the most important prognostic factors associated with recurrence in PCs, independent of histologic type.

Pro Inflammatory Cytokines Profiles of Patients With Long COVID Differ Between Variant Epochs.

BACKGROUND: Over 30% of patients with COVID-19 have persistent symptoms that last beyond 30 days and referred to as Long COVID. Long COVID has been associated with a persistent elevation in peripheral cytokines including interleukin-6, interleukin-1ß, and tumor necrosis factor-α. This study reports cytokine profiles of patients in our clinic across SARS-COV-2 variant epochs. METHODS: The clinical cytokine panel was analyzed in patients with Long COVID during periods that were stratified according to variant epoch. The 4 variant epochs were defined as: (1) wild-type through alpha, (2) alpha/beta/gamma, (3) delta, and (4) omicron variants. RESULTS: A total of 390 patients had the clinical cytokine panel performed; the median age was 48 years (IQR 38-59) and 62% were female. Distribution by variant was wild-type and alpha, 50% (n = 196); alpha/beta/gamma, 7.9% (n = 31); delta, 18% (n = 72); and omicron, 23% (n = 91). Time to cytokine panel testing was significantly longer for the earlier epochs. Tumor necrosis factor-α (P < .001) and interleukin 1ß (P < .001) were significantly more elevated in the earlier epochs (median of 558 days in wild-type through Alpha epoch vs 263 days in omicron epoch, P < .001)). Nucleocapsid antibodies were consistently detected across epochs. DISCUSSION: When stratified by variant epoch, patients with early epoch Long COVID had persistently elevated peripheral pro-inflammatory cytokine levels when compared to later epoch Long COVID. Patients with Long COVID have similar clusters of symptoms across epochs, suggesting that the underlying pathology is independent of the peripheral cytokine signature.

Robotics in Massage: A Systematic Review.

Background: Over the past few years, a growing number of studies have explored massage robots. However, to date, a dedicated systematic review focused solely on robot-assisted massage has not been conducted. Objective: To systematically identify and summarize evidence from studies concerning robot-assisted massage in healthcare settings. Methods: An extensive literature search, involving electronic databases Ovid and Scopus, was conducted from the inception of the databases up to March 2023. This systematic review adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement, and relevant papers were chosen based on the predefined inclusion criteria. Given the substantial methodological diversity among the included studies, a qualitative analysis was conducted. Results: Seventeen studies met the inclusion criteria, comprising 15 preliminary trials, one quasi-experimental study, and one randomized controlled trial. Approximately 29% of the studies focused on the application of robotic massage for patients, 24% targeted both healthy volunteers and patients, and the remaining 47% were preclinical trials assessing the effectiveness of robotic massage solely on healthy volunteers. Primary interventions included robotic massage for oral rehabilitation, scalp massage, low back massage, shoulder massage, and full-body massage. All studies provided evidence that robotic massage interventions can enhance health and well-being, indicating a promising future for the integration of robotics in the field of massage therapy. Conclusions: In general, robotic massage interventions offer physical and mental health benefits. Robot-assisted massage may be integrated into care provision as an adjunct to enhance human well-being. Nonetheless, further research is needed to confirm these findings.

Longitudinal Progression of Patients with Long COVID Treated in a Post-COVID Clinic: A Cross-Sectional Survey.

BACKGROUND: In addition to the morbidity and mortality associated with acute infection, COVID-19 has been associated with persistent symptoms (>30 days), often referred to as Long COVID (LC). LC symptoms often cluster into phenotypes, resembling conditions such as fibromyalgia, postural orthostatic tachycardiac syndrome (POTS), and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). LC clinics have been established to best address the needs of LC patients and continuity of care. We developed a cross-sectional survey to assess treatment response through our LC Clinic (LCC). METHODS: A 25-question survey (1-10 Likert scale) was expert- and content-validated by LCC clinicians, patients, and patient advocates. The survey assessed LC symptoms and the helpfulness of different interventions, including medications and supplements. A total of 852 LCC patients were asked to complete the survey, with 536 (62.9%) responding. RESULTS: The mean time from associated COVID-19 infection to survey completion was 23.2 ± 6.4 months. The mean age of responders was 52.3 ± 14.1 (63% females). Self-reported symptoms were all significantly improved (P < .001) from the initial visit to the LCC (baseline) to the time of the follow-up survey. However, only 4.5% (24/536) of patients rated all symptoms low (1-2) at the time of the survey, indicating low levels of full recovery in our cohort. The patients rated numerous interventions as being helpful, including low-dose naltrexone (45/77; 58%), vagal nerve stimulation (18/34; 53%), and fisetin (28/44; 64%). CONCLUSIONS: Patients report general improvements in symptoms following the initial LCC visit, but complete recovery rates remain low at 23.2 ± 6.4 months.

Perioperative cardiac risk reduction in non cardiac surgery.

For patients undergoing nonemergent noncardiac surgery, care must be taken to identify patients at increased risk of major adverse cardiovascular events, as these remain a significant source of perioperative morbidity and mortality. Identification of at-risk patients requires careful attention to risk factors including assessment of functional status, medical comorbidities, and a medication assessment. After identification, to minimize perioperative cardiac risk, care should be taken through a combination of appropriate medication management, close monitoring for cardiovascular ischemic events, and optimization of pre-existing medical conditions. There are multiple society guidelines that aim to mitigate risk of cardiovascular morbidity and mortality in patients undergoing nonemergent noncardiac surgery. However, the rapid evolution of medical literature often creates gaps between the existing evidence and best practice recommendations. In this review, we aim to reconcile the recommendations made in the guidelines from the major cardiovascular and anesthesiology societies from the USA, Canada, and Europe, and to provide updated recommendations based on new evidence.

Post-COVID Conditions.

Postinfectious syndromes have been described since the Spanish influenza pandemic of 1918. A similar syndrome-post-COVID condition (PCC)-is common; it occurs months after COVID-19 infection and involves fatigue, postexertional malaise, dyspnea, memory loss, diffuse pain, and orthostasis. The medical, psychosocial, and economic impact of PCC is immense. In the United States, PCC has caused widespread unemployment and billions in lost wages. Risk factors for development of PCC are female sex and severity of acute COVID-19 infection. Proposed pathophysiologic mechanisms include central nervous system inflammation, viral reservoirs, persistent spike protein, cell receptor dysregulation, and autoimmunity. Because presenting symptoms are often vague, the approach to evaluation should be comprehensive with consideration of other diseases that could masquerade as PCC. Treatments of PCC are little researched, are largely expert based, and are likely to evolve as more evidence emerges. Current therapies, which are symptom targeted, include medications and nonpharmacologic therapies such as optimizing fluid intake, compression garments, progressive activity, meditation, biofeedback, cognitive rehabilitation, and addressing concomitant mood disorders. Many patients will enjoy significant improvements in their quality of life with multimodal treatments and longitudinal care.

Inflammatory Arthritis After COVID-19: A Case Series.

BACKGROUND Some patients who have recovered from acute infection with SARS-CoV-2 develop persistent symptoms that have been termed post-COVID syndrome (PoCoS). PoCoS can affect the musculoskeletal system, with arthralgia and myalgia being common. Preliminary evidence suggests that PoCoS is an immune-mediated condition that not only predisposes but also precipitates pre-existing inflammatory joint diseases such as rheumatoid arthritis and reactive arthritis. Here, we describe a series of patients who presented to our Post-COVID Clinic and were found to have inflammatory arthritis (reactive and rheumatoid arthritis). CASE REPORT We present 5 patients who developed joint pain several weeks after recovery from acute SARS-CoV-2 infection. These patients were seen in our Post-COVID Clinic and came from locations across the United States. All 5 patients were women, with age of diagnosis of COVID-19 disease between 19 and 61 years (mean 37.8 years). All patients presented with joint pain as the primary concern to the Post-COVID Clinic. Abnormal joint imaging was present in all patients. Treatments varied and included non-steroidal anti-inflammatory drugs, acetaminophen, corticosteroids, immunomodulators (golimumab), methotrexate, leflunomide, and hydroxychloroquine. CONCLUSIONS COVID-19 disease is a potential cause of inflammatory arthritis, with both rheumatoid arthritis and reactive arthritis demonstrated in our PoCoS population. Care must be taken to identify these conditions, as there are treatment ramifications.

Satisfaction and Feasibility Evaluation of an Electronic Massager-Expert Manipulative Massage Automation (EMMA): A Pilot Study.

BACKGROUND: Electronic massagers have gained popularity for their non-invasive and cost-effective approach to healthcare. However, existing electronic massagers require manual manipulation, leading to inconsistency. OBJECTIVE: To investigate the feasibility and acceptability of the Electronic Massager-Expert Manipulative Massage Automation (EMMA) among the American population. METHODS: A single-arm pilot study was conducted at Mayo Clinic Rochester campus. Participants received massage therapy with the EMMA treatment model and completed a demographics and Satisfaction Survey Questionnaire. Data were collected using REDCap, and statistical analysis was performed. RESULTS: Twenty healthy volunteers (13 women, 7 men; median age, 47 years) participated and completed the intervention within 2 weeks. No adverse events were reported. Overall, the acceptability and satisfaction of massage utilizing EMMA were high, with all participants finding the study worthwhile, willing to participate again, and willing to recommend the study to others. Regarding the overall experience, 65.0% reported a better-than-expected experience. Responses to open-ended post-treatment questions showed that most participants enjoyed the warmth (35%), pressure (25%), and relaxation (20%) provided by EMMA, with the majority suggesting no changes or improvements were needed. However, some participants expressed a desire for an expanded massage area (20%). CONCLUSIONS: This study suggests that the EMMA massager has high acceptability and satisfaction among healthy volunteers, thus demonstrating its feasibility. However, further research is needed to optimize EMMA and assess its clinical effectiveness.

Cardiopulmonary testing in long COVID-19 versus non-COVID-19 patients with undifferentiated Dyspnea on exertion.

BACKGROUND: Dyspnea and fatigue are characteristics of long SARS-CoV-2 (COVID)-19. Cardiopulmonary exercise testing (CPET) can be used to better evaluate such patients. RESEARCH QUESTION: How significantly and by what mechanisms is exercise capacity impaired in patients with long COVID who are coming to a specialized clinic for evaluation? STUDY DESIGN AND METHODS: We performed a cohort study using the Mayo Clinic exercise testing database. Subjects included consecutive long COVID patients without prior history of heart or lung disease sent from the Post-COVID Care Clinic for CPET. They were compared to a historical group of non-COVID patients with undifferentiated dyspnea also without known cardiac or pulmonary disease. Statistical comparisons were performed by t-test or Pearson's chi2 test controlling for age, sex, and beta blocker use where appropriate. RESULTS: We found 77 patients with long COVID and 766 control patients. Long COVID patients were younger (47 ± 15 vs 50 ± 10 years, P < .01) and more likely female (70% vs 58%, P < .01). The most prominent difference on CPETs was lower percent predicted peak V̇O2 (73 ± 18 vs 85 ± 23%, p < .0001). Autonomic abnormalities (resting tachycardia, CNS changes, low systolic blood pressure) were seen during CPET more commonly in long COVID patients (34 vs 23%, P < .04), while mild pulmonary abnormalities (mild desaturation, limited breathing reserve, elevated V̇E/V̇CO2) during CPET were similar (19% in both groups) with only 1 long COVID patient showing severe impairment. INTERPRETATION: We identified severe exercise limitation among long COVID patients. Young women may be at higher risk for these complications. Though mild pulmonary and autonomic impairment were common in long COVID patients, marked limitations were uncommon. We hope our observations help to untangle the physiologic abnormalities responsible for the symptomatology of long COVID.

Multimodal Treatment of Malignant Pleural Mesothelioma: Real-World Experience with 112 Patients.

Malignant pleural mesothelioma (MPM) is a rare pleural cancer associated with asbestos exposure. According to current evidence, the combination of chemotherapy, surgery and radiotherapy improves patients' survival. However, the optimal sequence and weighting of the respective treatment modalities is unclear. In anticipation of the upcoming results of the MARS-2 trial, we sought to determine the relative impact of the respective treatment modalities on complications and overall survival in our own consecutive institutional series of 112 patients. Fifty-seven patients (51%) underwent multimodality therapy with curative intent, while 55 patients (49%) were treated with palliative intent. The median overall survival (OS) of the entire cohort was 16.9 months (95% CI: 13.4−20.4) after diagnosis; 5-year survival was 29% for patients who underwent lung-preserving surgery. In univariate analysis, surgical treatment (p < 0.001), multimodality therapy (p < 0.001), epithelioid subtype (p < 0.001), early tumor stage (p = 0.02) and the absence of arterial hypertension (p = 0.034) were found to be prognostic factors for OS. In multivariate analysis, epithelioid subtype was associated with a survival benefit, whereas the occurrence of complications was associated with worse OS. Multimodality therapy including surgery significantly prolonged the OS of MPM patients compared with multimodal therapy without surgery.

The Female-Predominant Persistent Immune Dysregulation of the Post-COVID Syndrome.

OBJECTIVE: To describe the clinical data from the first 108 patients seen in the Mayo Clinic post-COVID-19 care clinic (PCOCC). METHODS: After Institutional Review Board approval, we reviewed the charts of the first 108 patients seen between January 19, 2021, and April 29, 2021, in the PCOCC and abstracted from the electronic medical record into a standardized database to facilitate analysis. Patients were grouped into phenotypes by expert review. RESULTS: Most of the patients seen in our clinic were female (75%; 81/108), and the median age at presentation was 46 years (interquartile range, 37 to 55 years). All had post-acute sequelae of SARS-CoV-2 infection, with 6 clinical phenotypes being identified: fatigue predominant (n=69), dyspnea predominant (n=23), myalgia predominant (n=6), orthostasis predominant (n=6), chest pain predominant (n=3), and headache predominant (n=1). The fatigue-predominant phenotype was more common in women, and the dyspnea-predominant phenotype was more common in men. Interleukin 6 (IL-6) was elevated in 61% of patients (69% of women; P=.0046), which was more common than elevation in C-reactive protein and erythrocyte sedimentation rate, identified in 17% and 20% of cases, respectively. CONCLUSION: In our PCOCC, we observed several distinct clinical phenotypes. Fatigue predominance was the most common presentation and was associated with elevated IL-6 levels and female sex. Dyspnea predominance was more common in men and was not associated with elevated IL-6 levels. IL-6 levels were more likely than erythrocyte sedimentation rate and C-reactive protein to be elevated in patients with post-acute sequelae of SARS-CoV-2 infection.

Systemic lupus erythematosus multiorgan flare with quiescent serologic markers.

Systemic lupus erythematosus (SLE) can affect almost every organ with differing degrees of severity. Typically, SLE activity is associated with hypocomplimentaemia and elevated double-stranded DNA (dsDNA) levels. We describe a case of a severe multiorgan lupus flare including lupus cerebritis, autoimmune haemolytic anaemia, lupus nephritis and lupus myopericarditis with normal complement and dsDNA levels. This highlights the importance of understanding the heterogeneous nature of SLE flares.

Transporting Children to Safety After Volcanic Eruption.

The Fuego volcano eruption near Guatemala City, Guatemala, on June 3, 2018, left more than 150 dead and hundreds more injured or missing. Local officials quickly identified a need for burn care among the injured and asked the international community for assistance. By the morning of June 4, members of the U.S. Army's Burn Flight Team were placed on high alert in preparation for an evacuation mission to bring injured Guatemalans to the United States for specialized burn care. The mission required seven RNs, three respiratory therapists, a burn surgeon, two intensivists, an anesthesiologist, and an operations officer in order to successfully evacuate six critically injured pediatric burn patients to the Shriners Hospitals for Children-Galveston in Galveston, Texas. This article describes details of each stage of the mission and includes a discussion of key aspects of logistics and patient care posed by such evacuations.

Transcription factors sp1 and sp3 regulate expression of human extracellular superoxide dismutase in lung fibroblasts.

The molecular mechanisms that govern the transcription of human extracellular superoxide dismutase (EC-SOD), the major extracellular antioxidant enzyme, are largely unknown. To elucidate the mechanisms involved in human EC-SOD gene regulation and expression, we localized multiple transcription start sites to a finite region located 3.9 kb upstream of the ATG initiation codon. Within this segment, we subcloned a 2.7-kb fragment upstream of a luciferase reporter gene; the resulting construct exhibited strong in vivo promoter activity in two lung-derived cell lines. Deletion analysis of the EC-SOD 5'-flanking sequences identified a minimal 0.3-kb region that had strong basal promoter activity. Computer sequence analysis revealed a putative Sp1-like binding site within the EC-SOD proximal promoter region that lacked a TATA-box and showed a high frequency of GC nucleotides. Binding of Sp1 and Sp3 transcription factors to the EC-SOD promoter was confirmed by DNase I footprint analysis, electophoretic mobility shift assay, and competition and supershift assays. Cotransfection of the EC-SOD promoter-luciferase reporter constructs with plasmids encoding Sp1 and Sp3 into Sp-deficient insect SL2 cells showed strong activation of luciferase gene expression. The occupancy of the EC-SOD promoter by Sp1/Sp3 and RNA polymerase II in vivo was determined by chromatin immunoprecipitation assay and correlated well with levels of EC-SOD expression in lung epithelial cells (A549) and pulmonary fibroblasts (MRC5). Collectively, our results demonstrate the important role Sp1 and Sp3 plays in regulating the expression of human EC-SOD in the lung.

Rare Cause of Recurrent Pneumonia in the Left Lower Lobe.

A 52-year-old male patient was hospitalized in our department with the diagnosis of recurrent pneumonia in the left lower lobe. The patient reported possible aspiration of plastic material about 10 years ago, although repeated bronchoscopies in an external hospital had not revealed any foreign body. A multiply folded 8-cm filing strip for a ring folder was detected and successfully removed together with granulation tissue by means of rigid bronchoscopy.

Comparison of in vitro closure time (PFA-100) with whole blood electrical aggregometry and platelet surface antigen expression in healthy volunteers.

It was the aim of this study to compare in vitro closure time (PFA-100), reflecting platelet-related primary hemostasis, to more platelet-specific tests like whole blood electrical aggregometry and platelet surface antigen expression in healthy volunteers. In vitro closure time was measured using a PFA-100. Platelet surface antigen expression (CD63, CD62-P, CD42b, CD36, CD31) was determined in accordance with the consensus protocol for flow-cytometric characterisation of platelet function. Platelet aggregometry was performed using a whole blood electrical aggregometer (ADP and arachidonic acid as agonists). Analysis of the obtained data revealed only a few significant correlations between the different platelet function tests used. This finding can be explained by the various aspects of platelet function being focused by these tests in different extents. Whenever platelet function is analysed, the investigator should be aware of the specific and limited evidence of the method used. For screening purposes, it may be useful to introduce a platelet function index, referring to basal platelet activity, platelet adhesion and platelet aggregation at low and high shear stress forces.

Serum concentration of integrin-linked kinase in malignant pleural mesothelioma and after asbestos exposure.

OBJECTIVES: Integrin-linked kinase (ILK) is an intracellular protein implicated in chronic inflammation and neoplastic transformation. In a recently accomplished pilot study, we showed that ILK can be detected in the serum of patients with benign and malignant chest diseases, including malignant pleural mesothelioma (MPM). Interestingly, average serum ILK concentrations were 10 times higher in MPM patients when compared with the rest of the study population, and a diagnostic test solely based on serum ILK concentration could discriminate between MPM and non-MPM with considerable accuracy. This study aimed to investigate whether serum ILK concentration could also be used to discriminate between MPM and asbestos exposure only. METHODS: Using a self-developed sandwich enzyme-linked immunosorbent assay, we measured serum ILK concentrations in 101 MPM patients, and 96 asbestos-exposed, but healthy insulation workers. Seventy-three MPM patients had an epitheloid subtype (72.3%), and 42 had a Stage I or II disease (41.6%). RESULTS: When compared with asbestos-exposed individuals, MPM patients of all clinical stages had significantly higher (mean ± standard deviation, median) serum ILK concentrations (10.7 ± 13.6, median 7 ng/ml vs 3.1 ± 4.6, median 1.4 ng/ml; P < 0.001). Among MPM patients, the serum ILK concentration was significantly higher at advanced disease stages III + IV than at early stages I + II (13.7 ± 15.9, median 8.5 ng/ml vs 6.7 ± 7.8, median 3.5 ng/ml; P = 0.02). Using serum ILK to discriminate between MPM patients and asbestos-exposed individuals yielded an area under the curve of 0.69 (95% confidence interval 0.63-0.76). The corresponding sensitivity and specificity for a cut-off of 4.49 ng/ml ILK are 61.4 and 80.2%, respectively. CONCLUSIONS: These data show significant differences between MPM patients and asbestos-exposed but healthy individuals concerning their serum ILK concentration. Furthermore, since ILK levels are increased in advanced MPM stages in comparison with early MPM stages, we suggest evaluating its potential use as a marker of disease progression in MPM.