Thoracic Anesthesia during the COVID-19 Pandemic: 2021 Updated Recommendations by the European Association of Cardiothoracic Anaesthesiology and Intensive Care (EACTAIC) Thoracic Subspecialty Committee.

The novel coronavirus pandemic has radically changed the landscape of normal surgical practice. Lifesaving cancer surgery, however, remains a clinical priority, and there is an increasing need to fully define the optimal oncologic management of patients with varying stages of lung cancer, allowing prioritization of which thoracic procedures should be performed in the current era. Healthcare providers and managers should not ignore the risk of a bimodal peak of mortality in patients with lung cancer; an imminent spike due to mortality from acute coronavirus disease 2019 (COVID-19) infection, and a secondary peak reflecting an excess of cancer-related mortality among patients whose treatments were deemed less urgent, delayed, or cancelled. The European Association of Cardiothoracic Anaesthesiology and Intensive Care Thoracic Anesthesia Subspecialty group has considered these challenges and developed an updated set of expert recommendations concerning the infectious period, timing of surgery, vaccination, preoperative screening and evaluation, airway management, and ventilation of thoracic surgical patients during the COVID-19 pandemic.

Thoracic Anesthesia of Patients With Suspected or Confirmed 2019 Novel Coronavirus Infection: Preliminary Recommendations for Airway Management by the European Association of Cardiothoracic Anaesthesiology Thoracic Subspecialty Committee.

The novel coronavirus has caused a pandemic around the world. Management of patients with suspected or confirmed coronavirus infection who have to undergo thoracic surgery will be a challenge for the anesthesiologists. The thoracic subspecialty committee of European Association of Cardiothoracic Anaesthesiology (EACTA) has conducted a survey of opinion in order to create recommendations for the anesthetic approach to these challenging patients. It should be emphasized that both the management of the infected patient with COVID-19 and the self-protection of the anesthesia team constitute a complicated challenge. The text focuses therefore on both important topics.

Anesthetic considerations for tracheobronchial resection in oncologic surgery.

PURPOSE OF REVIEW: Anesthesia for the resection and reconstruction of the tracheobronchial tree for neoplastic disease is challenging, both from surgical as well as anesthetic points of view. There are no published recommendations or guidelines addressing anesthetic and airway management dilemmas that arise during these surgical interventions. This review presents key aspects of preoperative imaging evaluation, surgical planning, as well as anesthesia and airway management during these complex cases. RECENT FINDINGS: Newly published articles highlight both the surgical and anesthetic challenges encountered during tracheobronchial resections and emphasize the importance of creating specialized, high-volume centers for good patient outcomes. Of great importance is the development of a preoperative joint anesthetic-surgical plan which includes a patient-specific airway management strategy. This review presents newer and less commonly employed anesthetic management strategies which have been recently described in the literature to allow expansion of care to patients who were previously deemed too high risk for surgery. SUMMARY: With advances in technology, the use of classical ventilation methods in conjunction with newer alternatives, such as extracorporeal membrane oxygenation, creates the premise for a more individualized, safer and controlled approach to tracheobronchial resections for oncologic purposes.

ALS/FTD-associated FUS activates GSK-3ß to disrupt the VAPB-PTPIP51 interaction and ER-mitochondria associations.

Defective FUS metabolism is strongly associated with amyotrophic lateral sclerosis and frontotemporal dementia (ALS/FTD), but the mechanisms linking FUS to disease are not properly understood. However, many of the functions disrupted in ALS/FTD are regulated by signalling between the endoplasmic reticulum (ER) and mitochondria. This signalling is facilitated by close physical associations between the two organelles that are mediated by binding of the integral ER protein VAPB to the outer mitochondrial membrane protein PTPIP51, which act as molecular scaffolds to tether the two organelles. Here, we show that FUS disrupts the VAPB-PTPIP51 interaction and ER-mitochondria associations. These disruptions are accompanied by perturbation of Ca(2+) uptake by mitochondria following its release from ER stores, which is a physiological read-out of ER-mitochondria contacts. We also demonstrate that mitochondrial ATP production is impaired in FUS-expressing cells; mitochondrial ATP production is linked to Ca(2+) levels. Finally, we demonstrate that the FUS-induced reductions to ER-mitochondria associations and are linked to activation of glycogen synthase kinase-3ß (GSK-3ß), a kinase already strongly associated with ALS/FTD.

Comparative Study of Early Postoperative Complications: Thoracic Anastomosis vs Cervical Anastomosis - in Esophageal Replacement with Gastric Graft.

Gastric pull-up is the most commonly used procedure for esophageal replacement in both malignant and benign conditions. In our article we compare the differences in mortality and morbidity between thoracic anastomosis and cervical anastomosis during gastric pull-up. The study group comprised of 126 patients - 58 patients (56%) with cervical anastomosis and 68 patients (64%) with thoracic anastomosis. The overall mortality in the study group was 5.55% (7 patients), while the overall morbidity was higher at 28%. There were no significant differences between the two subgroups regarding mortality and morbidity, although the rate of anastomotic leakage was higher in the cervical subgroup (13.8% vs 1.5%). We recommend performing thoracic anastomosis during gastric pull-up whenever the location of the lesion allows it, since the procedure is safe, relatively easy to master and it shortens operating time by excluding the cervical approach.

α-Synuclein binds to the ER-mitochondria tethering protein VAPB to disrupt Ca2+ homeostasis and mitochondrial ATP production.

α-Synuclein is strongly linked to Parkinson's disease but the molecular targets for its toxicity are not fully clear. However, many neuronal functions damaged in Parkinson's disease are regulated by signalling between the endoplasmic reticulum (ER) and mitochondria. This signalling involves close physical associations between the two organelles that are mediated by binding of the integral ER protein vesicle-associated membrane protein-associated protein B (VAPB) to the outer mitochondrial membrane protein, protein tyrosine phosphatase-interacting protein 51 (PTPIP51). VAPB and PTPIP51 thus act as a scaffold to tether the two organelles. Here we show that α-synuclein binds to VAPB and that overexpression of wild-type and familial Parkinson's disease mutant α-synuclein disrupt the VAPB-PTPIP51 tethers to loosen ER-mitochondria associations. This disruption to the VAPB-PTPIP51 tethers is also seen in neurons derived from induced pluripotent stem cells from familial Parkinson's disease patients harbouring pathogenic triplication of the α-synuclein gene. We also show that the α-synuclein induced loosening of ER-mitochondria contacts is accompanied by disruption to Ca2+ exchange between the two organelles and mitochondrial ATP production. Such disruptions are likely to be particularly damaging to neurons that are heavily dependent on correct Ca2+ signaling and ATP.

Effects of logging on roadless space in intact forest landscapes of the Congo Basin.

Forest degradation in the tropics is often associated with roads built for selective logging. The protection of intact forest landscapes (IFL) that are not accessible by roads is high on the biodiversity conservation agenda and a challenge for logging concessions certified by the Forest Stewardship Council (FSC). A frequently advocated conservation objective is to maximize the retention of roadless space, a concept that is based on distance to the nearest road from any point. We developed a novel use of the empty-space function - a general statistical tool based on stochastic geometry and random sets theory - to calculate roadless space in a part of the Congo Basin where road networks have been expanding rapidly. We compared the temporal development of roadless space in certified and uncertified logging concessions inside and outside areas declared IFL in 2000. Inside IFLs, road-network expansion led to a decrease in roadless space by more than half from 1999 to 2007. After 2007, loss leveled out in most areas to close to 0 due to an equilibrium between newly built roads and abandoned roads that became revegetated. However, concessions in IFL certified by FSC since around 2007 continuously lost roadless space and reached a level comparable to all other concessions. Only national parks remained mostly roadless. We recommend that forest-management policies make the preservation of large connected forest areas a top priority by effectively monitoring - and limiting - the occupation of space by roads that are permanently accessible.

Postintubation Tracheoesophageal Fistula - Diagnosis, Treatment and Prognosis.

Introduction: Postintubation tracheoesophageal fistula is a severe complication occurring under certain conditions in patients that require prolonged mechanical ventilation. MATERIAL AND METHODS: This article focuses on a sample of 11 patients with postintubation tracheoesophageal fistula, operated in our department between 2005 and 2015. The anterior approach with tracheal resection was performed in 10 of these patients, while an atypical surgical technique was preferred in a case involving a large-sized fistula. Three of these patients were subject to surgery while still on the ventilator, in order to help weaning them from mechanical ventilation. Two patients were operated following a relapse of the fistula, after attempts of closing it in other surgical units. Results: Two patients (of those who were still on mechanical ventilation) died from intubation-related complications that persisted after tracheal resection (anastomotic dehiscence with mediastinitis and tracheoarterial fistula in the brachiocephalic arterial trunk). The nine remaining patients improved, with their airways restored and having regained normal deglutition. Conclusions: The surgical approach of this pathology is successful in surgical units that are specialised in tracheal and oesophageal surgery. Adequately timing the surgery is crucial for a good outcome.

VAPB interacts with the mitochondrial protein PTPIP51 to regulate calcium homeostasis.

A proline to serine substitution at position 56 in the gene encoding vesicle-associated membrane protein-associated protein B (VAPB) causes some dominantly inherited familial forms of motor neuron disease including amyotrophic lateral sclerosis (ALS) type-8. VAPB is an integral endoplasmic reticulum (ER) protein whose amino-terminus projects into the cytosol. Overexpression of ALS mutant VAPBP56S disrupts ER structure but the mechanisms by which it induces disease are not properly understood. Here we show that VAPB interacts with the outer mitochondrial membrane protein, protein tyrosine phosphatase-interacting protein 51 (PTPIP51). ER and mitochondria are both stores for intracellular calcium (Ca(2+)) and Ca(2+) exchange between these organelles occurs at regions of ER that are closely apposed to mitochondria. These are termed mitochondria-associated membranes (MAM). We demonstrate that VAPB is a MAM protein and that loss of either VAPB or PTPIP51 perturbs uptake of Ca(2+) by mitochondria following release from ER stores. Finally, we demonstrate that VAPBP56S has altered binding to PTPIP51 and increases Ca(2+) uptake by mitochondria following release from ER stores. Damage to ER, mitochondria and Ca(2+) homeostasis are all seen in ALS and we discuss the implications of our findings in this context.

A Multi-Country Survey on the Availability of Intraoperative Use of Echocardiography for Noncardiac Surgery.

BACKGROUND: This survey aimed to explore the availability and accessibility of echocardiography during noncardiac surgery worldwide. METHODS: An internet-based 45-item survey was sent, followed by reminders from August 30, 2021, to August 20, 2022. RESULTS: 1189 responses were received from 62 countries. Nearly seventy-one percent of respondents had intraoperatively used transesophageal or transthoracic echocardiography (TEE and TTE, respectively) for monitoring or examination. The unavailability of echocardiography machines (30.3%), lack of trained personnel (30.2%), and absence of clinical indications (22.6%) were the top 3 reasons for not using intraoperative echocardiography in noncardiac surgery. About 61.5% of participants had access to at least one echocardiography machine. About 41% had access to at least 1 TEE probe, and 62.2% had access to at least 1 TTE probe. Seventy-four percent of centers had a procedure to request intraoperative echocardiography if needed for noncardiac cases. Intraoperative echocardiography service was immediately available in 58% of centers. CONCLUSIONS: Echocardiography machines and skilled echocardiographers are still unavailable at many centers worldwide. National societies should aim to train a critical mass of certified TEE/TTE anesthesiologists and provide all anesthesiologists access to perioperative TEE/TTE machines in anesthesiology departments, considering the increasing number of older and sicker surgical patients scheduled for noncardiac surgery.

A Rare Thymic Tumor - Lipofibroadenoma - Always a Postoperative Surprise.

BACKGROUND/AIM: Thymic lipofibroadenoma is a benign growth of unknown etiology extremely rarely described in the literature, morphologically resembling lipofibroadenoma of the breast. The diagnosis is usually a postoperative surprise and is made by the anatomopathologist. Surgical resection is curative. CASE REPORT: The presented case is the first reported in a woman, to date. The patient was successfully submitted to surgery and complete resection of the giant intrathoracic tumor was performed. The histopathological and immunohistochemical studies came to demonstrated the presence of a thymic lipofibroadenoma while the postoperative outcomes were favorable. CONCLUSION: In cases presenting large intrathoracic tumors complete resection is able to provide a significant improvement of the general condition of the patient, as well as a chance for cure.

Post-Pneumonectomy ARDS and Ogilvie Syndrome - A Case Report.

INTRODUCTION: The Acute Respiratory Distress Syndrome (ARDS) is a severe hypoxemic acute lung injury that may complicate lung resections. Reported mortality is very high, up to 50%. This report covers an ARDS case occurring post left pneumonectomy, with a favorable outcome, despite association with an acute colonic pseudo-obstruction syndrome (Ogilvie syndrome) that required abdominal surgery for decompression. CASE REPORT: A 60-year old Caucasian male, diagnosed with a stage IIIA left lung tumor underwent a left pneumonectomy. On the second postoperative day, the patient developed ARDS, requiring ventilatory support. Two days later, as the multiple organ dysfunction worsened, a bowel obstruction occurred. With an acute colonic pseudo-obstruction diagnosis, the decision was to perform laparotomy and a temporary cecostomy. A subsequent improvement in the respiratory parameters and vital functions resulted in weaning from ventilator 8 days after the onset of the ARDS and transfer to the surgery ward 14 days after pneumonectomy.

Disruption of ER-mitochondria signalling in fronto-temporal dementia and related amyotrophic lateral sclerosis.

Fronto-temporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) are two related and incurable neurodegenerative diseases. Features of these diseases include pathological protein inclusions in affected neurons with TAR DNA-binding protein 43 (TDP-43), dipeptide repeat proteins derived from the C9ORF72 gene, and fused in sarcoma (FUS) representing major constituent proteins in these inclusions. Mutations in C9ORF72 and the genes encoding TDP-43 and FUS cause familial forms of FTD/ALS which provides evidence to link the pathology and genetics of these diseases. A large number of seemingly disparate physiological functions are damaged in FTD/ALS. However, many of these damaged functions are regulated by signalling between the endoplasmic reticulum and mitochondria, and this has stimulated investigations into the role of endoplasmic reticulum-mitochondria signalling in FTD/ALS disease processes. Here, we review progress on this topic.

Species persistence decreases with habitat fragmentation: an analysis in periodic stochastic environments.

This paper presents a study of a nonlinear reaction-diffusion population model in fragmented environments. The model is set on R(N), with periodic heterogeneous coefficients obtained using stochastic processes. Using a criterion of species persistence based on the notion of principal eigenvalue of an elliptic operator, we provided a precise numerical analysis of the interactions between habitat fragmentation and species persistence. The obtained results clearly indicated that species persistence strongly tends to decrease with habitat fragmentation. Moreover, comparing two stochastic models of landscape pattern generation, we observed that in addition to local fragmentation, a more global effect of the position of the habitat patches also influenced species persistence.

The ER-Mitochondria Tethering Complex VAPB-PTPIP51 Regulates Autophagy.

Mitochondria form close physical associations with the endoplasmic reticulum (ER) that regulate a number of physiological functions. One mechanism by which regions of ER are recruited to mitochondria involves binding of the ER protein VAPB to the mitochondrial protein PTPIP51, which act as scaffolds to tether the two organelles. Here, we show that the VAPB-PTPIP51 tethers regulate autophagy. We demonstrate that overexpression of VAPB or PTPIP51 to tighten ER-mitochondria contacts impairs, whereas small interfering RNA (siRNA)-mediated loss of VAPB or PTPIP51 to loosen contacts stimulates, autophagosome formation. Moreover, we show that expression of a synthetic linker protein that artificially tethers ER and mitochondria also reduces autophagosome formation, and that this artificial tether rescues the effects of siRNA loss of VAPB or PTPIP51 on autophagy. Thus, these effects of VAPB and PTPIP51 manipulation on autophagy are a consequence of their ER-mitochondria tethering function. Interestingly, we discovered that tightening of ER-mitochondria contacts by overexpression of VAPB or PTPIP51 impairs rapamycin- and torin 1-induced, but not starvation-induced, autophagy. This suggests that the regulation of autophagy by ER-mitochondria signaling is at least partly dependent upon the nature of the autophagic stimulus. Finally, we demonstrate that the mechanism by which the VAPB-PTPIP51 tethers regulate autophagy involves their role in mediating delivery of Ca2+ to mitochondria from ER stores. Thus, our findings reveal a new molecular mechanism for regulating autophagy.

Hepatopulmonary syndrome: an unusual cause of dyspnea in the pulmonology ward - case presentation.

Hepatopulmonary syndrome is one of the possible complications of chronic liver disease, defined clinically by impaired oxygenation. The underlying cause of the respiratory failure is the presence of intrapulmonary shunting, as a result of abnormal vascular dilatations in the lungs. We report the case of 52-year-old male, exsmoker, with a history of pulmonary TB and also of heavy drinking, who was admitted to the pulmonology ward for dyspnea at rest and limb cyanosis. His clinical exam was suggestive of liver cirrhosis, with signs of pneumonia, but also chronic lung disease. Variations in SaO2 with posture were noted: platypnea and orthodeoxia. Arterial gas assessment revealed severe hypoxemia, only partially corrected by high-flow oxygen therapy, while plethysmography showed only a mild obstructive syndrome, but with severely impaired alveolar-capillary diffusion. The suspicion of a hepatopulmonary syndrome was raised and a contrast echocardiography confirmed the diagnosis by revealing the presence of an intrapulmonary shunt. Although it is believed to be a fairly common complication of chronic liver disease, it is possible for a case of hepatopulmonary syndrome to be admitted solely for respiratory symptoms. The patient's poor socio-economic status is the main reason for both the lack of proper followup for his liver disease and the limited therapeutic options. Keywords: Hepatopulmonary syndrome, liver cirrhosis, respiratory failure, contrast echocardiography

There's Something Wrong with my MAM; the ER-Mitochondria Axis and Neurodegenerative Diseases.

Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis with associated frontotemporal dementia (ALS/FTD) are major neurodegenerative diseases for which there are no cures. All are characterised by damage to several seemingly disparate cellular processes. The broad nature of this damage makes understanding pathogenic mechanisms and devising new treatments difficult. Can the different damaged functions be linked together in a common disease pathway and which damaged function should be targeted for therapy? Many functions damaged in neurodegenerative diseases are regulated by communications that mitochondria make with a specialised region of the endoplasmic reticulum (ER; mitochondria-associated ER membranes or 'MAM'). Moreover, several recent studies have shown that disturbances to ER-mitochondria contacts occur in neurodegenerative diseases. Here, we review these findings.

Nodular pulmonary amyloidosis--rare cause of calcified pulmonary nodules.

The article presents the case of a 60-year-old asymptomatic woman whose chest X-ray screening showed bilateral pulmonary nodules of uncertain etiology. Initially, the main suspicion concerned multiple pulmonary metastases, but the anatomical pathology examination of two of the surgically removed lung nodules revealed a benign pattern--foreign body granulomatous reaction to cholesterol crystals. Patient follow-up with a repeat computed tomography one year later showed that some pulmonary nodules had slightly increased in number and size, so the diagnosis required re-evaluation. Congo red staining revealed a positive reaction in the amorphous material, pointing to a nodular form of pulmonary amyloidosis. This case attests to the wide range of investigations needed to examine multiple pulmonary nodules and to the great variety of possible diagnoses. Surgical biopsy, alongside histopathological examination and immunohistochemical tests of the lung are critical in establishing a positive diagnosis. Pulmonary amyloidosis requires additional investigations and long-term follow-up of the patient, as this condition is frequently associated with MALT (mucosa-associated lymphoid tissue) lymphoma or multiple myeloma.

[Tracheal resection for post-intubation subglottic stenosis in a patient with granulomatosis with polyangiitis (Wegener)]. / Rezectie de trahee pentru stenoza subglotica post-intubatie la o pacienta cu granulomatoza cu poliangeita (Wegener).

Granulomatosis with polyangiitis (GPA or Wegener) is a systemic autoimmune disease with inflammation of small- and medium-size vessels. It can affect practically any organ or system, but renal, respiratory andjoint systems are most frequently damaged. Positive pANCA antibodies can raise the suspicion of diagnosis. Subglottic stenosis is relatively frequent, in a quarter of patients, especially in the third decade women. The case presented is of an 80-year-old woman, recently diagnosed with pulmonary, renal and systemic manifestations of GPA and with a subglottic stenosis rapidly evolving towards endotracheal intubation, tracheostomy with mechanical ventilation and renal failure. Further evolution has been favorable under corticoid therapy. After weaning from the mechanical ventilation and30 days after the suppression of the tracheostomy, the patient developed a tracheal stenosis with mixed etiology, secondary to vasculitis and prolonged intubation with tracheostomy. Tracheal resection with termino-terminal anastomosis was performed in emergency with simple post-operative evolution and without late complications.

[Delayed diagnosis in a case of granulomatosis with polyangiitis (Wegener's) with initial predominance of joint involvement]. / Diagnostic tardiv într-un caz de granulomatoza cu poliangeita (Wegener) cu manifestari initiale articulare.

The authors present the case of a 53-year-old female, initially admitted in a rheumatology department for fever and diffuse arthritis--being diagnosed with sero-positive rheumathoid arthritis. Although the chest X-ray and CT scan of thorax showed several abnormal features (medium lobe atelectasis, pseudo-cyst in the posterior segment of the right upper lobe with satellite milliary nodules, mediastinal lymph node enlargement), the investigations performed in our pneumology department couldn't establish the etiology of radiological abnormalities. With non-steroidal antiinflamatory treatment, the patient got worse, being readmitted in our hospital after 3 months for high fever, diffuse arthralgia with functional impairment, small hemoptysis, loss of hearing and left ear ache and on chest X-ray with bilateral macronodules, some of these with cavitation. The investigations showed a slight alveolar hemorrhagic syndrome, positive cANCA antibodies, negative antiCCP antibodies--the diagnosis of Wegener's granulomatosis with lung and ENT involvement being established. Puls-therapy with Solumedrol and i.v. Cyclophosphamide was thereafter initiated with a favorable evolution. This case is special because of the initial misdiagnosis due to the atypical pulmonary manifestations and the non-specific paraclinical findings, in the context of diffuse arthritis with positive rheumatoid factor.