The Genes-Stemness-Secretome Interplay in Malignant Pleural Mesothelioma: Molecular Dynamics and Clinical Hints.

MPM has a uniquely poor somatic mutational landscape, mainly driven by environmental selective pressure. This feature has dramatically limited the development of effective treatment. However, genomic events are known to be associated with MPM progression, and specific genetic signatures emerge from the exceptional crosstalk between neoplastic cells and matrix components, among which one main area of focus is hypoxia. Here we discuss the novel therapeutic strategies focused on the exploitation of MPM genetic asset and its interconnection with the surrounding hypoxic microenvironment as well as transcript products and microvesicles representing both an insight into the pathogenesis and promising actionable targets.

Radiofrequency stimulation of the dorsal root ganglion as a diagnostic tool for radicular pain syndromes: six representative cases.

BACKGROUND: We discuss the diagnostic benefit of pulsed radiofrequency (PRF) of the dorsal root ganglion (DRG) in a case series of patients with different pathologies. We expand the diagnostic potential of DRG stimulation beyond paresthesia mapping by using DRG stimulation to help determine the role of the DRG in the patient's pain and narrow down the etiology. In some cases, DRG stimulation was also part of the treatment plan. METHODS: Six patients underwent DRG radiofrequency as a diagnostic/therapeutic step before considering implantation of a DRG neurostimulator. First, patients underwent a basic bedside neurological evaluation. Next, an electrode was placed in the epidural space through the sacral hiatus or between vertebral laminae. Then, sensory stimulation was applied at 50 Hz and gradually increased from 0.1 V until the patient reported paresthesia or until a maximum intensity of 2 V was reached. Patients were asked to describe where the stimulation was felt and outline the anatomical area the paresthesia covered. Then a motor stimulation was applied at 2 Hz until muscle twitching was reported by the patient or observed by the physician. RESULTS: The information obtained helped diagnose the type of lesion as principally preganglionic, ganglionic, or postganglionic. This information guided patient management. CONCLUSION: PRF of the DRG can provide valuable diagnostic information and is a useful step before ganglionic electrode implantation. In all cases, PRF of the DRG provided valuable diagnostic information and guided management options.

Emergency Awake Laparotomy Using Neuraxial Anaesthesia: A Case Series and Literature Review.

Emergency laparotomy is a surgical procedure associated with significantly higher mortality rates compared to elective surgeries. Awake laparotomy under neuraxial anaesthesia has recently emerged as a promising approach in abdominal surgery to improve patient outcomes. This study aims to evaluate the feasibility and potential benefits of using neuraxial anaesthesia as the primary anaesthetic technique in emergency laparotomies. We conducted a case series involving 16 patients who underwent emergency laparotomy for bowel ischemia, perforation, or occlusion. Neuraxial anaesthesia was employed as the main anaesthetic technique. We analysed patient demographics, clinical characteristics, intraoperative details, and postoperative outcomes. The primary outcome measures included the adequacy of postoperative pain control, the incidence of postoperative complications, and mortality rates. Among the 16 patients, adequate postoperative pain control was achieved, with only 2 patients requiring additional analgesia. Postoperative complications, including sepsis, wound dehiscence, and pneumonia, were observed in seven patients (44%). The observed mortality rate was relatively low at 6% (one patient). Notably, conversion to general anaesthesia was not necessary in any of the cases, and no early readmissions were reported. Our findings highlight the feasibility and potential benefits of using neuraxial anaesthesia in emergency laparotomies. The observed low mortality rate and the avoidance of conversion to general anaesthesia suggest that neuraxial anaesthesia may be a useful alternative in emergency settings. However, the occurrence of postoperative complications in 44% of patients indicates the need for cautious patient selection and close monitoring. Further research with larger sample sizes is warranted to fully elucidate the efficacy, safety, and potential impact of this technique on patient outcomes in emergency laparotomies.

Transforaminal Steroid Injection After Dorsal Root Ganglion Pulsed Radiofrequency (DRG-PRF): Impact on Pain Intensity and Disability.

INTRODUCTION: Dorsal root ganglion pulsed radiofrequency (DRG-PRF) is frequently used for the treatment of chronic lumbar radicular pain with good outcomes in terms of pain management. Transforaminal epidural steroid injection (TFESI) is often administered immediately after DRG-PRF to increase the anti-inflammatory effects, but support for the synergic mechanism is lacking in the literature. The aim of this study was to investigate the potential role of TFESI immediately after DRG-PRF and its possible role on pain intensity and patient disability. METHODS: A database of patients who underwent DRG-PRF with or without TFESI immediately after DRG-PRF was retrospectively analysed; propensity score matching was applied to the analysis to reduce possible bias. Pain intensity (numerical rating scale [NRS]) and Oswestry disability index (ODI) were recorded pre-operatively and at the 1- and 3-month follow-up in the two groups of patients. RESULTS: A total of 252 patients were included in this retrospective analysis, 126 patients in the DRG-PRF + TFESI group and 126 patients in the DRG-PRF group after propensity score matching. Both groups displayed a significant reduction in pain intensity (NRS score reduction; p < 0.0001) and improvement in the ODI (p < 0.0001) from baseline at the 3-month follow-up. Interestingly, the use of TFESI after DRG-PRF was not associated with any clinical benefit as no difference in NRS and ODI was found between the two groups at the 1- and 3-month follow-ups. CONCLUSIONS: Our study revealed a significant pain reduction and disability improvement after DRG-PRF in patients with lumbar radicular pain. Interestingly, no positive role of TFESI immediately after DRG-PRF was observed. These findings suggest that DRG-PRF provides substantial pain relief, and no added benefit is obtained with subsequent steroid injection. Future prospective studies with expanded follow-up periods are needed to confirm these findings.

Left atrium veno-arterial extra corporeal membrane oxygenation as temporary mechanical support for cardiogenic shock: A case report.

BACKGROUND: Veno-arterial extra corporeal membrane oxygenation (VA-ECMO) support is commonly complicated with left ventricle (LV) distension in patients with cardiogenic shock. We resolved this problem by transeptally converting VA-ECMO to left atrium veno-arterial (LAVA)-ECMO that functioned as a temporary paracorporeal left ventricular assist device to resolve LV distension. In our case LAVA-ECMO was also functioning as a bridge-to-transplant device, a technique that has been scarcely reported in the literature. CASE SUMMARY: A 65 year-old man suffered from acute myocardial injury that required percutaneous stents. Less than two weeks later, noncompliance to antiplatelet therapy led to stent thrombosis, cardiogenic shock, and cardiac arrest. Femoro-femoral VA-ECMO support was started, and the patient underwent a second coronary angiography with re-stenting and intra-aortic balloon pump placement. The VA-ECMO support was complicated by left ventricular distension which we resolved via LAVA-ECMO. Unfortunately, episodes of bleeding and sepsis complicated the clinical picture and the patient passed away 27 d after initiating VA-ECMO. CONCLUSION: This clinical case demonstrates that LAVA-ECMO is a viable strategy to unload the LV without another invasive percutaneous or surgical procedure. We also demonstrate that LAVA-ECMO can also be weaned to a left ventricular assist device system. A benefit of this technique is that the procedure is potentially reversible, should the patient require VA-ECMO support again. A transeptal LV venting approach like LAVA-ECMO may be indicated over ImpellaTM in cases where less LV unloading is required and where a restrictive myocardium could cause LV suctioning. Left ventricular over-distention is a well-known complication of peripheral VA-ECMO in cardiogenic shock and LAVA ECMO through transeptal cannulation offers a novel and safe approach for treating LV overloading, without the need of an additional percutaneous access.

Smoking Habit and Respiratory Function Predict Patients' Outcome after Surgery for Lung Cancer, Irrespective of Histotype and Disease Stage.

BACKGROUND: Growing evidence suggests that sublobar resections offer more favorable outcomes than lobectomy in early-stage lung cancer surgery. However, a percentage of cases that cannot be ignored develops disease recurrence irrespective of the surgery performed with curative intent. The goal of this work is thus to compare different surgical approaches, namely, lobectomy and segmentectomy (typical and atypical) to derive prognostic and predictive markers. PATIENTS AND METHODS: Here we analyzed a cohort of 153 NSCLC patients in clinical stage TNM I who underwent pulmonary resection surgery with a mediastinal hilar lymphadenectomy from January 2017 to December 2021, with an average follow-up of 25.5 months. Partition analysis was also applied to the dataset to detect outcome predictors. RESULTS: The results of this work showed similar OS between lobectomy and typical and atypical segmentectomy for patients with stage I NSCLC. In contrast, lobectomy was associated with a significant improvement in DFS compared with typical segmentectomy in stage IA, while in stage IB and overall, the two treatments were similar. Atypical segmentectomy showed the worst performance, especially in 3-year DFS. Quite unexpectedly, outcome predictor ranking analysis suggests a prominent role of smoking habits and respiratory function, irrespective of the tumor histotype and the patient's gender. CONCLUSIONS: Although the limited follow-up interval cannot allow conclusive remarks about prognosis, the results of this study suggest that both lung volumes and the degree of emphysema-related parenchymal damage are the strongest predictors of poor survival in lung cancer patients. Overall, these data point out that greater attention should be addressed to the therapeutic intervention for co-existing respiratory diseases to obtain optimal control of early lung cancer.

Malignant Pleural Mesothelioma: Genetic and Microenviromental Heterogeneity as an Unexpected Reading Frame and Therapeutic Challenge.

Mesothelioma is a malignancy of serosal membranes including the peritoneum, pleura, pericardium and the tunica vaginalis of the testes. Malignant mesothelioma (MM) is a rare disease with a global incidence in countries like Italy of about 1.15 per 100,000 inhabitants. Malignant Pleural Mesothelioma (MPM) is the most common form of mesothelioma, accounting for approximately 80% of disease. Although rare in the global population, mesothelioma is linked to industrial pollutants and mineral fiber exposure, with approximately 80% of cases linked to asbestos. Due to the persistent asbestos exposure in many countries, a worldwide progressive increase in MPM incidence is expected for the current and coming years. The tumor grows in a loco-regional pattern, spreading from the parietal to the visceral pleura and invading the surrounding structures that induce the clinical picture of pleural effusion, pain and dyspnea. Distant spreading and metastasis are rarely observed, and most patients die from the burden of the primary tumor. Currently, there are no effective treatments for MPM, and the prognosis is invariably poor. Some studies average the prognosis to be roughly one-year after diagnosis. The uniquely poor mutational landscape which characterizes MPM appears to derive from a selective pressure operated by the environment; thus, inflammation and immune response emerge as key players in driving MPM progression and represent promising therapeutic targets. Here we recapitulate current knowledge on MPM with focus on the emerging network between genetic asset and inflammatory microenvironment which characterize the disease as amenable target for novel therapeutic approaches.

Brown recluse (L. rufescens) can bite in Northern Italy, too: first case report and review of the literature.

The brown recluse, or fiddleback (violin) spider, is a poisonous spider of the Loxosceles genus that resides in warmer regions and old structures making the warm Mediterranean climate a natural habitat for the European species, L. rufescens Even in infested households, however, bites are rare, as they are nocturnal and unaggressive. In 2015, the first supposed death by L. rufescens occurred in Italy, but before and even after such bite, the literature on these spiders has been under-represented. This case report documents a confirmed bite by a violin spider on a medical student in Pavia, Italy. The presentation in this case was initially with general systemic, flu-like symptoms, then as cellulitis with lymphangitis that persisted for nearly 2 weeks until resolving without prolonged or complicated pathology. We present the first documented case of a L. rufescens bite in Northern Italy, to the best of our knowledge.