Chronic Thromboembolic Pulmonary Hypertension after Pulmonary Embolism in SARS-CoV-2.

INTRODUCTION: Chronic thromboembolic pulmonary disease (CTEPD) consists of persistent pulmonary vascular obstruction on imaging and involves long-term functional limitations, with or without chronic thromboembolic pulmonary hypertension (CTEPH). The aim of this study was to evaluate the incidence and risk factors of both persistent pulmonary vascular defects and CTEPH after hospitalization in patients with COVID-19 and PE during a 2-year follow-up. METHODS: A prospective observational study was carried out in a tertiary hospital center. Patients were hospitalized between March 2020 and December 2021 with a diagnosis of PE during SARS-CoV-2 infection. Patients received anticoagulant treatment for at least 3 months and were followed up for 2 years. Between the third and fourth months after discharge, all patients were evaluated for the presence of residual thrombotic defects by CTPA and/or perfusion pulmonary scintigraphy. Clinical findings, lung function tests with DLCO, exercise capacity, and echocardiograms were also assessed. RESULTS: Of the 133 patients included, 18% had persistent thrombotic defects on lung imaging at follow-up. The incidence of CTEPD was 0.75% at 2 years of follow-up. Patients with persistent defects were significantly older, had a higher prevalence of systemic arterial hypertension, higher D-dimer and NT-proBNP levels, and more severe PE at diagnosis. Furthermore, there was a higher prevalence of right ventricular dysfunction on echocardiogram at diagnosis of PE (25.0% vs. 2.7%, p = 0.006). This was the only variable independently related to persistent defects in multivariate analyses (OR: 8.13 [95% CI: 1.82-36.32], p = 0.006). CONCLUSION: The persistence of thrombotic defects after PE is a common finding after SARS-CoV-2 infection, affecting 18% of the population. However, the incidence of CTEPH appears to be lower (0.75%) in COVID-19-related PE compared to that previously observed in PE unrelated to COVID-19.

A model for ribosome translocation based on the alternated displacement of its subunits.

A meaningful dilemma in ribosome translocation arising from experimental facts is that, although the ribosome-mRNA interaction force always has a significant magnitude, the ribosome still moves to the next codon on the mRNA. How does the ribosome move to the next codon in the sequence while holding the mRNA tightly? The hypothesis proposed here is that ribosome subunits alternate the grip of the ribosome on the mRNA, freeing the other subunit of such interaction for a while, thus allowing its motion to the following codon. Based on this assumption, a single-loop cycle of ribosome configurations involving the relative position of its subunits is elaborated. When its dynamic is modeled as a Markov network, it gives expressions for the average ribosome translocation speed and stall force as functions of the equilibrium constants among the proposed ribosome configurations. The calculations have a reasonable agreement with experimental results, and the succession of molecular events considered here is consistent with current biomolecular concepts of the ribosome translocation process. Thus, the alternative displacements hypothesis developed in the present work suggests a feasible explanation of ribosome translocation.

Lymph node metastasis in level IIb in oropharyngeal squamous cell carcinoma: a multicentric, longitudinal, retrospective analysis.

INTRODUCTION: Nowadays, 70% of patients in Europe and the USA are affected by a p16 + , potentially HPV driven oropharyngeal squamous cell carcinoma. However, despite the improved survival rate in this group, the quality-of-life remains low in cases which neck dissection took place. In this vein, in recent years, some surgeons have considered to avoid dissection of level IIB, proposing a supra-selective non-IIb neck dissection. MATERIALS AND METHODS: A retrospective, longitudinal, multicentric study was conducted, including patients with pathologically confirmed primary HPV + or HPV - OPSCC who went through surgical treatment for the primary lesion and neck dissection. RESULTS: 141 patients were included. Among them, 99 (70.2%) were male and 42 (29.8%) were female. The mean age was 62 ± 9 years (range 36-81). The most frequent anatomical location was the tonsil in 63 (44.7%) of patients. The most common approach was the classic transoral oropharyngectomy in 51 (36.2%) patients. Immunohistochemistry for p16 was positive in 62 (44%) patients. One-hundred and five (74.5%) patients received a unilateral ND, and a 36 (25.5%) a bilateral ND. Of those, a 12.8% (18/141) of patients were level IIb LN + . According to our results, level IIb ND should be considered in patients underwent therapeutic ND with positive LN metastasis in level IIa (OR = 9.83; 95% CI 3.463-27.917) or III (OR = 6.25; 95% CI 2.158-18.143), advanced (T3/T4) oropharyngeal primary tumors (OR = 3.38; 95% CI 1.366-8.405), and patients with ENE (OR = 6.56; 95% CI 2.182-19.770), regardless of p16 status. CONCLUSIONS: According to our results, level IIb ND should be considered in patients who underwent therapeutic ND with positive LN metastasis in level IIa or III, advanced oropharyngeal primary tumors, and patients with ENE, independently of p16 status. Prospective data are necessary to definitively ensure the safety of omitting ipsilateral or contralateral level IIb ND in cN - patients with early stage disease.

Complications related to the Cook-Swartz implantable Doppler probe use in head and neck microvascular reconstruction: a systematic review.

PURPOSE: Vascular perfusion research has been dedicated to identify inexpensive, effective, and easy to use methods to assess free flap perfusion for both buried and non-buried flaps. METHODS: Systematic review of complications in patients underwent Head and Neck microsurgical reconstruction and vascular implantable Doppler monitoring. RESULTS: Sixteen articles were included for qualitative analysis. 2535 (92.2%) patients received IDP monitorization. Venous thrombosis was the most common vascular complication effecting 28 (1.1%). Regarding complications potentially related to the use of the IDP, just one study described the presence of granuloma formation along the suture line in 2 (0.07%) patients. CONCLUSIONS: Our findings indicated that Cook-Swartz IDP will represents a safe and effective device for FF monitoring in HN reconstructive micro-surgery. A detailed prospective registration of the results and complications related to the use of IDP remains mandatory to precisely estimate results, cost, and complications.

Machine Learning Models for Predicting Facial Nerve Palsy in Parotid Gland Surgery for Benign Tumors.

BACKGROUND: Despite the increasing use of intraoperative facial nerve monitoring during parotid gland surgery (PGS) and the improvement in the preoperative radiological assessment, facial nerve injury (FNI) remains the most severe complication after PGS. Until now, no studies have been published regarding the application of machine learning (ML) for predicting FNI after PGS. We hypothesize that ML would improve the prediction of patients at risk. METHODS: Patients who underwent PGS for benign tumors between June 2010 and June 2019 were included. RESULTS: Regarding prediction accuracy and performance of each ML algorithm, the K-nearest neighbor and the random forest achieved the highest sensitivity, specificity, positive predictive value, negative predictive value F-score, receiver operating characteristic (ROC)-area under the ROC curve, and accuracy globally. The K-nearest neighbor algorithm achieved performance values above 0.9 for specificity, negative predictive value, F-score and ROC-area under the ROC curve, and the highest sensitivity and positive predictive value. CONCLUSIONS: This study demonstrates that ML prediction models can provide evidence-based predictions about the risk of FNI to otolaryngologists and patients. It is hoped that such algorithms, which use clinical, radiological, histological, and cytological information, can improve the information given to patients before surgery so that they can be better informed of any potential complications.

Stochastic microswimming model of ribosome motion on the polysome.

In this work we assume that the ribosome propels itself during the translocation step of the translation process of protein synthesis by running a cycle of stochastically generated conformational changes involving its two subunits. This cycle includes only two experimentally found ribosome shape changes. The main result is an analytic expression for ribosome's average swimming speed on a polysome, where the ribosome is in the presence of other ribosomes. Relevant geometric parameters of ribosome deformations are calculated first by solving a deterministic problem where the ribosome runs a cycle of prescribed conformational changes. The method of reflections and pairwise additivity are used to obtain the stresses and forces needed to apply the multiparticle reciprocal theorem. Ribosome's average velocity when it runs the corresponding stochastic cycle of deformations is calculated assuming independence among the conformational cycles of different ribosomes on the polysome. The results obtained show that swimming in tandem on the polysome allows the ribosome to reach any typical subcellular speed with deformations whose amplitude is of a smaller size than when it swims alone in the fluid. Also, the flow organized by its swimming stroke becomes more determinant for its motion than random diffusion, compared to the solitary ribosome.

Sialendoscopy-assisted transoral approach for parotid gland lithiasis.

INTRODUCTION: Although lithiasis represents more than 60% of all cases of salivary gland obstruction, only 20% occurs in the Stensen´s duct. Nonetheless, the potential complications related to parotid gland surgery due to facial nerve injury, makes the development of minimally invasive techniques highly relevant. MATERIALS AND METHODS: A pilot study was conducted to assess results of patients treated by sialendoscopy-assisted trans-oral approach to treat Stensen´s duct lithiasis. RESULTS: Eight patients were included; all of them operated satisfactorily. Six of them were male, and 2 were female. The mean size of the stones was 9.6 mm (Min: 6 mm/Max: 16 mm). Regarding to lithiasis location: it was anterior to the masseter line in the distal third of the Stensen's duct in seven patients and in another patient was immediately below the buccinator muscle. During the follow-up, all patients presented a healthy functioning of the gland after the compressive massage. Regarding complications, one patient presented a Stensen's duct stenosis, which required reintervention. CONCLUSION: The transoral Stensen´s duct approach represents a safe technique for lithiasis bigger than 3 mm in the distal portion of the Stensen´s duct, anterior to the Masseter Muscle line and when other minimal invasive techniques fail.

Predictive factors for simultaneous distant metastasis in head and neck cancer patients during the diagnostic work-up.

INTRODUCTION: The incidence of distant metastasis (DM) in patients affected by head and neck squamous cell carcinoma (HNSCC) is relatively low, and multiple risk factors were described for the development of distant metastasis. MATERIALS AND METHODS: Retrospective study of patients diagnosed with a HNSCC between July 2016 and July 2020 in a tertiary university hospital. RESULTS: Five-Hundred and sixty-nine patients meet inclusion criteria. In the univariate analysis we found a statistical correlation in those patients affected by a hypopharyngeal tumour (p = < 0.0001), patients older than 60 years old (p = 0.01), advanced T stage (p = < 0.0001), a proven positive lymph node (p = 0.02), poorly differentiated tumour (p = < 0.0001), patients with 3 or more positive lymph nodes (p = 0.0001), with ECS (p = 0.0001) and a second primary tumour (p = 0.03). However, according to those results from our multivariable analysis, the factor related to an increased or higher chance to detect a DM during the diagnosis work-up were the presence of a hypopharyngeal primary tumor with a hazard ratio (HR) of 1.14, p = < 0.0001, advanced T stage (T3-T4) with a HR of 1.21, p = 0.001, poorly differentiated tumor with a HR of 1.04, p = < 0.0001, have proven positive lymph node with a HR of 1.03, p = 0.04, have more than three positive lymph node metastases with a HR of 1.25, p = 0.003, the presence of ECS with a HR of 1.40, p = 0.002, and have a second primary tumor with a HR of 1.05, p = 0.01. CONCLUSION: According to the present study, factors such as hypopharyngeal tumours, advanced T-stage, poor differentiation grade, have more than three positive lymph nodes, ECS and have a second primary tumour should be considered as high-risk indicators for screening. Based on these results, the authors recommend considered an extensive diagnostic work-up in all patients with a high risk of DM development.

Complications after Functional Neck Dissection in Head and Neck Cancer Patients: An Observational, Retrospective, Single-Centre Study.

INTRODUCTION: Functional neck dissection (FND) represents a surgical procedure usually associated with less morbidity. METHODS: An observational, retrospective, analysis of patients diagnosed with any type of head and neck malignancy was designed to summarize and report the incidence of postoperative complications in patients undergoing FND including just those levels described for selective neck dissections in a tertiary university hospital between June 2016 and June 2019. RESULTS: 131 patients met the inclusion criteria. The total number of sides studied was 200. 40.5% of the patients suffer a complication in the postoperative period, being the spinal accessory nerve (SAN) injury the most common complication (10%). We did not find any statistical -correlation between the previous organ-preservation treatments and surgical complications (p = 0.207). An advanced T stage (p = 0.009) and the need of bilateral FND (p = 0.034) were significantly correlated with a higher risk of surgical complications. CONCLUSION: FND represents a useful technique. In this study, 40.5% of the patients suffer a complication in the postoperative period, being the SAN injury the most common complication. However, these data contribute to increasing our knowledge about surgical complications related to FND.

Imaging checklist for preoperative evaluation of laryngeal tumors to be treated by transoral microsurgery: guidelines from the European Laryngological Society.

INTRODUCTION: The modern availability in daily practice of different DICOM viewers allows physicians to routinely evaluate computed tomography (CT) and magnetic resonance (MR) scans of patients in the pre-, intra-, and postoperative settings. Their systematic use, together with a close surgeon-radiologist cooperation, may greatly improve outcomes of patients to be treated by transoral microsurgery for laryngeal cancer. MATERIALS AND METHODS: We herein propose guidelines for systematic evaluation of CT/MR images taken from patients affected by supraglottic and glottic cancer to be treated by transoral microsurgery. RESULTS: A methodical, step-by-step approach focused on laryngeal anatomy, systematically looking at each true and false vocal folds, anterior commissure, laryngeal ventricle, subglottic area, epiglottis, thyroid, cricoid, and arytenoid cartilages, posterior commissure, crico-arytenoid unit, paraglottic and pre-epiglottic spaces, and possible extra-laryngeal extension is proposed. This checklist may be useful before imaging performance (to focus on specific issues to be detailed by the radiologist), as well before and during surgery for the specific evaluation of details to be cleared during transoral microsurgery. CONCLUSION: Detailed preoperative evaluation of supraglottic and glottic anatomy is essential prior to any transoral approach for neoplastic disease. The proposed imaging checklist described herein represents a step-by-step guide to surgeons performing this kind of interventions and an aid in achieving a meticulous approach from a surgical perspective.

Translation and validation of the Parotidectomy Outcome Inventory 8 (POI-8) to Spanish.

INTRODUCTION: There are >400 million of native Spanish speakers around the world, being the second most spoken language in regard to the number of native speakers. For this reason, a valid questionnaire to access the quality of our patients after parotidectomy is necessary. MATERIAL AND METHODS: Validation and cross-cultural adaptation of the POI-8 questionnaire to the Spanish language. Internal consistency of Sp-POI 8 measured with Cronbach α. RESULTS: 35 patients met the inclusion criteria during the mentioned period. Mean age was 59 ±â€¯15,37 (Min: 18/Max: 87). 20 patients (57,1%) were male and 15 (42,9%) were female. Internal consistency with Cronbach α was 0.868. The intraclass correlation coefficient was 0.830 [CI] (95%: 0,791-925). Hypoesthesia was the most severely weighted problem (0,91) and xerostomia was the second (0,89). However, the high score was for fear of revision surgery (1,26). CONCLUSION: The Spanish Language is the second most spoken language with regard to the number of native speakers and the Sp-POI 8 translation represents a valid option for the Spanish-speaking medical community, from which a large number of patients can benefit.

Porcine experimental model for perforator flap raising in reconstructive microsurgery.

BACKGROUND: Perforator free flap-based reconstruction of the head and neck is a challenging surgical procedure and needs a steep learning curve. A reproducible mammal large animal model with similarities to human anatomy is relevant for perforator flap raising and microanastomosis. The aim of this study was to assess the feasibility of a swine model for perforator-based free flaps in reconstructive microsurgery. METHODS: Eleven procedures were performed under general anesthesia in a porcine model, elevating a skin flap vascularized by perforating musculocutaneous branches of the superior epigastric artery to evaluate the relevance of this model for head and neck reconstructive microsurgery. RESULTS: The anterior abdominal skin perforator-based free flap in a swine model irrigated by the superior epigastric artery was elevated in eleven procedures. In six of these procedures, we could perform an arterial and venous microanastomosis to the great vessels located in the base of the neck. CONCLUSIONS: The porcine experimental model of superior epigastric artery perforator-based free flap reconstruction offers relevant similarities to the human deep inferior epigastric artery perforator flap. We could demonstrate this model as acceptable for perforator free flap training due to the necessity of perforator and pedicle dissection and transfer to a distant area.

The dynamics of MAPK inactivation at fertilization in mouse eggs.

Egg activation at fertilization in mammals is initiated by prolonged Ca(2+) oscillations that trigger the completion of meiosis and formation of pronuclei. A fall in mitogen-activated protein kinase (MAPK) activity is essential for pronuclear formation, but the precise timing and mechanism of decline are unknown. Here, we have measured the dynamics of MAPK pathway inactivation during fertilization of mouse eggs using novel chemiluminescent MAPK activity reporters. This reveals that the MAPK activity decrease begins during the Ca(2+) oscillations, but MAPK does not completely inactivate until after pronuclear formation. The MAPKs present in eggs are Mos, MAP2K1 and MAP2K2 (MEK1 and MEK2, respectively) and MAPK3 and MAPK1 (ERK1 and ERK2, respectively). Notably, the MAPK activity decline at fertilization is not explained by upstream destruction of Mos, because a decrease in the signal from a Mos-luciferase reporter is not associated with egg activation. Furthermore, Mos overexpression does not affect the timing of MAPK inactivation or pronuclear formation. However, the late decrease in MAPK could be rapidly reversed by the protein phosphatase inhibitor, okadaic acid. These data suggest that the completion of meiosis in mouse zygotes is driven by an increased phosphatase activity and not by a decline in Mos levels or MEK activity.

Theoretical estimate of the effect of thermal agitation on ribosome motion generated by stochastic microswimming.

The effect of thermal agitation on ribosome motion is evaluated through the Péclet number, assuming that the ribosome is self-propelled along the mRNA during protein synthesis by a swimming stroke consisting of a cycle of stochastically-generated ribosome configurations involving its two subunits. The ribosome velocity probability distribution function is obtained, giving an approximately normal distribution. Its mean and variance together with an estimate of the in vivo free diffusion coefficient of the ribosome and using only configuration changes of small size, give a Péclet number similar to motor proteins and microorganisms. These results suggest the feasibility of the stochastic microswimming hypothesis to explain ribosome motion.

Polymorphisms in alcohol and tobacco metabolism genes in head and neck cancer in the Basque Country.

BACKGROUND: The Basque Country has one of the highest rates of head and neck squamous cell carcinoma (HNSCC) in Europe, although tobacco and alcohol consumption are not high when compared to other European countries where HNSCC incidence is lower. Our aim was to determine the role of genetic variation with regard to the metabolism of alcohol and carcinogens from tobacco smoke in the Basque Country. METHODS: Fourteen polymorphisms in alcohol or tobacco metabolism genes were genotyped in 84 HNSCC patients and 242 healthy individuals from the Basque Country. RESULTS: ADH1B histidine allele (rs1229984), CYP2E1 rs3813867 heterozygous genotype, and GSTT1 deletion conferred protection against HNSCC (OR: 0.318 [0.04-0.75], OR: 0.13 [0.02-0.94], and OR: 0.12 [0.02-0.60], respectively) while GSTP1 (rs1695) Val/Val genotype was related to an increased risk (OR: 4.12 [1.11-15.31]). Regarding alcohol and tobacco habits, GSTT1 deletion was associated with tobacco usage, while the 3 polymorphisms tested in ALDH2 were associated with alcohol consumption. However, genotypic distributions of these 7 SNPs did not differ from those observed for other Caucasian populations where HNSCC incidence is lower. CONCLUSIONS: The identified genotypic variations in alcohol and tobacco metabolizing genes only by themselves do not seem to be responsible for the higher incidence of HNSCC observed in the Basque Country.

The dynamics of PKC-induced phosphorylation triggered by Ca2+ oscillations in mouse eggs.

Fertilization of mammalian eggs is characterized by a series of Ca(2+) oscillations triggered by a phospholipase C activity. These Ca(2+) increases and the parallel generation of diacylglycerol (DAG) stimulate protein kinase C (PKC). However, the dynamics of PKC activity have not been directly measured in living eggs. Here, we have monitored the dynamics of PKC-induced phosphorylation in mouse eggs, alongside Ca(2+) oscillations, using fluorescent C-kinase activity reporter (CKAR) probes. Ca(2+) oscillations triggered either by sperm, phospholipase C zeta (PLCζ) or Sr(2+) all caused repetitive increases in PKC-induced phosphorylation, as detected by CKAR in the cytoplasm or plasma membrane. The CKAR responses lasted for several minutes in both the cytoplasm and plasma membrane then returned to baseline values before subsequent Ca(2+) transients. High frequency oscillations caused by PLCζ led to an integration of PKC-induced phosphorylation. The conventional PKC inhibitor, Gö6976, could inhibit CKAR increases in response to thapsigargin or ionomycin, but not the repetitive responses seen at fertilization. Repetitive increases in PKCδ activity were also detected during Ca(2+) oscillations using an isoform-specific δCKAR. However, PKCδ may already be mostly active in unfertilized eggs, since phorbol esters were effective at stimulating δCKAR only after fertilization, and the PKCδ-specific inhibitor, rottlerin, decreased the CKAR signals in unfertilized eggs. These data show that PKC-induced phosphorylation outlasts each Ca(2+) increase in mouse eggs but that signal integration only occurs at a non-physiological, high Ca(2+) oscillation frequency. The results also suggest that Ca(2+) -induced DAG formation on intracellular membranes may stimulate PKC activity oscillations at fertilization.

Dual mechanism controls asymmetric spindle position in ascidian germ cell precursors.

Mitotic spindle orientation with respect to cortical polarity cues generates molecularly distinct daughter cells during asymmetric cell division (ACD). However, during ACD it remains unknown how the orientation of the mitotic spindle is regulated by cortical polarity cues until furrowing begins. In ascidians, the cortical centrosome-attracting body (CAB) generates three successive unequal cleavages and the asymmetric segregation of 40 localized postplasmic/PEM RNAs in germ cell precursors from the 8-64 cell stage. By combining fast 4D confocal fluorescence imaging with gene-silencing and classical blastomere isolation experiments, we show that spindle repositioning mechanisms are active from prometaphase until anaphase, when furrowing is initiated in B5.2 cells. We show that the vegetal-most spindle pole/centrosome is attracted towards the CAB during prometaphase, causing the spindle to position asymmetrically near the cortex. Next, during anaphase, the opposite spindle pole/centrosome is attracted towards the border with neighbouring B5.1 blastomeres, causing the spindle to rotate (10 degrees /minute) and migrate (3 microm/minute). Dynamic 4D fluorescence imaging of filamentous actin and plasma membrane shows that precise orientation of the cleavage furrow is determined by this second phase of rotational spindle displacement. Furthermore, in pairs of isolated B5.2 blastomeres, the second phase of rotational spindle displacement was lost. Finally, knockdown of PEM1, a protein localized in the CAB and required for unequal cleavage in B5.2 cells, completely randomizes spindle orientation. Together these data show that two separate mechanisms active during mitosis are responsible for spindle positioning, leading to precise orientation of the cleavage furrow during ACD in the cells that give rise to the germ lineage in ascidians.

Electrochemical degradation of trichloroacetic acid in aqueous media: influence of the electrode material.

The electrochemical degradation of trichloroacetic acid (TCAA) in water has been analysed through voltammetric studies with a rotating disc electrode and controlled-potential bulk electrolyses. The influence of the mass-transport conditions and initial concentration of TCAA for titanium, stainless steel and carbon electrodes has been studied. It is shown that the electrochemical reduction of TCAA takes place prior to the massive hydrogen evolution in the potential window for all electrode materials studied. The current efficiency is high (> 18%) compared with those normally reported in the literature, and the fractional conversion is above 50% for all the electrodes studied. Only dichloroacetic acid (DCAA) and chloride anions were routinely detected as reduction products for any of the electrodes, and reasonable values of mass balance error were obtained. Of the three materials studied, the titanium cathode gave the best results.

Transoral endoscopic ultrasonic surgery (TOUSS) in head & neck unknown primary carcinoma investigation.

Metastatic carcinoma of unknown primary (CUP) to cervical lymph nodes represents less than 5% of all head and neck malignancies. Recent publications support the use of transoral surgery during the diagnosis work-up, and transoral endoscopic ultrasonic surgery represent a recently described alternative technique in transoral surgery. A pilot study to assess the feasibility of trans-oral ultrasonic base of tongue (BOT) mucosectomy and bilateral tonsillectomy approach in CUP diagnosis work-up was conducted. Ten patients were included consecutively. In 2 cases (20%) the primary was found, in one case in the right tonsil, and another one in the left BOT. According to our results, the use of trans-oral ultrasonic surgery to perform the base of tongue mucosectomy and bilateral tonsillectomy in CUP patient's during the diagnosis work-up represents an effective option in patients with good anatomical exposure.