The Role of Pocus in Acute Respiratory Failure: A Narrative Review on Airway and Breathing Assessment.

Acute respiratory failure (ARF) is a challenging condition that clinicians, especially in emergency settings, have to face frequently. Especially in emergency settings, many underlying diseases can lead to ARF and life-threatening conditions have to be promptly assessed and correctly treated to avoid unfavorable outcomes. In recent years, point-of-care ultrasound (POCUS) gained growing consideration due to its bedside utilization, reliability and reproducibility even in emergency settings especially in unstable patients. Research on POCUS application to assess ARF has been largely reported mainly with observational studies showing heterogeneous results from many different applications. This narrative review describes the wide potentiality of POCUS to face airways and breathing life-threatening conditions such as upper airway management, pulmonary and pleural pathologies and diaphragm impairment. We conducted extensive research of the literature to report from major studies to case reports deemed useful in practical clinical utilization of POCUS in ARF. Due to the huge amount of the literature found, we focused on airways and breathing assessment trying to systematize the evidence according to clinical care of ARF in emergency settings. Further studies, possibly trials, should determine how POCUS is crucial in clinical practice in terms of standard of care improvements, patient safety and cost-benefit analysis.

Early sclerostin assessment in frail elderly patients with sepsis: insights on short- and long-term mortality prediction.

Unmet needs challenge clinical management of sepsis especially concerning patient profiling, enhancing recovery, and long-term sequelae. Here, we preliminarily focused on sclerostin (SOST) as a candidate biomarker to encompass such a broad range of clinical needs related to sepsis. Seventy-three septic patients were enrolled at internal medicine wards between January 2017 and December 2019 in this pilot study. Clinical examination and blood sample analyses were collected at enrollment and after 7 and 14 days. SOST levels were assessed on serum by ELISA. Thirty-day mortality was set as primary outcome. In-hospital and long-term mortality (2.5 years of median follow-up) were assessed as secondary outcomes. Patients were frail, elderly, and heterogeneous in terms of comorbidity burden. SOST levels were associated with age, cardiovascular comorbidities, and time to early death (30 days). When regression models were built, SOST displayed a high predictive value toward 30-day mortality (OR 13.459 with 95% CI 1.226-148.017) with ever better performance than validated scoring scales for critical ill patients. Such a predictive value of SOST was further confirmed for in-hospital (HR 10.089 with 95% CI 1.375-74.013) and long-term mortality (HR 5.061 with 95% CI 1.379-18.570). SOST levels generally decreased over 7 to 14 days after enrollment (p for trend < 0.001). The degree of this variation further predicted long-term mortality (HR for Δ SOST T0-day 14: 1.006 with 95% CI 1.001-1.011). Our results suggest a role for SOST in both short- and long-time prediction of worse outcome in septic elderly admitted to internal medicine wards.

Does Antithrombotic Therapy Affect Outcomes in Major Trauma Patients? A Retrospective Cohort Study from a Tertiary Trauma Centre.

Antithrombotic therapy may affect outcomes in major trauma but its role is not fully understood. We aimed to investigate adverse outcomes among those with and without antithrombotic treatment in major trauma. Material and methods: This is a retrospective study conducted at the Emergency Department (ED) of the University Hospital of Genoa, a tertiary trauma center, including all major trauma between January 2019 and December 2020. Adverse outcomes were reviewed among those without antithrombotic treatment (Group 0), on antiplatelet treatment (Group 1), and on anticoagulant treatment (Group 2). Results: We reviewed 349 electronic charts for full analysis. Group 0 were n = 310 (88.8%), Group 1 were n = 26 (7.4%), and Group 2 were n = 13 (3.7%). In-hospital death and ICU admission, respectively, were: n = 16 (5.6%) and n = 81 (26%) in Group 0, none and n = 6 (25%) in Group 1, and n = 2 (15.8%) and n = 4 (30.8%) in Group 2 (p = 0.123-p = 0.874). Altered INR (OR 5.2) and increasing D-dimer levels (AUC: 0.81) correlated to increased mortality. Discussion: Group 2 showed higher mortality than Group 0 and Group 1, however Group 2 had fewer active treatments. Of clotting factors, only altered INR and elevated D-dimer levels were significantly correlated to adverse outcomes. Conclusions: Anticoagulant but not antiplatelet treatment seems to produce the worst outcomes in major trauma.

Advanced Differentiated Thyroid Cancer: A Complex Condition Needing a Tailored Approach.

Differentiated thyroid cancers (DTCs) are slow-growing malignant tumours, including papillary and follicular carcinomas. Overall, prognosis is good, although it tends to worsen when local invasion occurs with bulky cervical nodes, or in the case of distant metastases. Surgery represents the main treatment for DTCs. However, radical excision is challenging and significant morbidity and functional loss can follow the treatment of the more advanced forms. Literature on advanced thyroid tumours, both differentiated and undifferentiated, does not provide clear and specific guidelines. This emerges the need for a tailored and multidisciplinary approach. In the present study, we report our single-centre experience of 111 advanced (local, regional, and distant) DTCs, investigating the rate of radical excision, peri-procedural and post-procedural complications, quality of life, persistence, recurrence rates, and survival rates. Results are critically appraised and compared to the existing published evidence review.

Conversion rates in robotic thyroid surgery: A systematic review and meta-analysis.

OBJECTIVE: To define the conversion risk to open procedure during robot-assisted thyroid surgery (RATS) identifying potential specific subclasses of procedures or accesses at higher conversion risk. METHODS: In a PRISMA-compliant framework, all original prospective studies providing RATS conversion rates from multiple databases were pooled in a random-effects meta-analysis. Conversion rates were compared between different typologies of thyroid surgery and robotic access. RESULTS: 13 studies were deemed eligible. Four conversions from two studies were reported out of 398 procedures. No significant heterogeneity was observed (Cochran's Q p = 0.932; I2 = 0%). The pooled conversion rate was 1% (95% confidence interval, 0.1%-2%). The ANOVA-Q test failed to show significant differences when comparing type of thyroid surgery or robotic access (respectively p = 0.766 and p = 0.457). CONCLUSION: While the conversion rate appears consistently low across studies, prospective data collection and systematic reporting of procedural complications are required for framing high-risk procedures and accesses.

Evidence of SARS-CoV-2 in nasal brushings and olfactory mucosa biopsies of COVID-19 patients.

The aim of the present study is to detect the presence of SARS-CoV-2 of patients affected by COVID-19 in olfactory mucosa (OM), sampled with nasal brushing (NB) and biopsy, and to assess whether a non-invasive procedure, such as NB, might be used as a large-scale procedure for demonstrating SARS-CoV-2 presence in olfactory neuroepithelium. Nasal brushings obtained from all the COVID-19 patients resulted positive to SARS-CoV-2 immunocytochemistry while controls were negative. Double immunofluorescence showed that SARS-CoV-2 positive cells included supporting cells as well as olfactory neurons and basal cells. OM biopsies showed an uneven distribution of SARS-CoV-2 positivity along the olfactory neuroepithelium, while OM from controls were negative. SARS-CoV-2 was distinctively found in sustentacular cells, olfactory neurons, and basal cells, supporting what was observed in NB. Ultrastructural analysis of OM biopsies showed SARS-CoV-2 viral particles in the cytoplasm of sustentacular cells. This study shows the presence of SARS-CoV-2 at the level of the olfactory neuroepithelium in patients affected by COVID-19. For the first time, we used NB as a rapid non-invasive tool for assessing a potential neuroinvasion by SARS-CoV-2 infection.

Choroidal vasculature analysis in MEK inhibitor-associated retinopathy.

PURPOSE: To evaluate choroidal vascularity index (CVI) in patients developing mitogen-activated protein kinase kinase (MEK) inhibitor-associated retinopathy (MEKAR). METHODS: In this prospective observational study, extensive ophthalmic examination was performed, including enhanced-depth-imaging-optical coherence tomography (EDI-OCT). EDI-OCT scans of patients receiving Cobimetinib, taken at baseline and at MEKAR manifestation, were considered for choroid analysis. Choroidal thickness (CT) was measured on high-resolution b-scans passing through the fovea at three different locations. Same scans were therefore imported for binarization into a previously reported software and CVI was calculated as the ratio of luminal area (LA) to total choroid area (TCA). RESULTS: When compared to baseline, eyes with MEKAR (14 eyes) did not show significative CT variation in subfoveal region (p = 0,57), 750-µm-nasal to the fovea (p = 0,08) and 750-µm-temporal to the fovea (p = 0,07). Similarly, there were no statistically significant differences for TCA (p = 0.54), LA (p = 0.85), stromal area (SA) (p = 0.13), LA/SA (p = 0.34) and CVI (p = 0.47). Best-corrected visual acuity was significantly reduced at fluid accumulation when compared to baseline values (p = 0.03), with complete recovery after fluid resolution (p = 0.73). CONCLUSION: Multiple parameters reflecting the status of the choroid seemed not influenced by Cobimetinib administration. Retinal pigment epithelium toxic disfunction likely represents the crucial step in MEKAR pathogenesis.

Adenoidectomy for middle ear disease in cleft palate children: a systematic review.

PURPOSE: Cleft palate children have a higher incidence of otitis media with effusion, more frequent recurrent acute otitis media episodes, and worse conductive hearing losses than non-cleft children. Nevertheless, data on adenoidectomy for middle ear disease in this patient group are scarce, since many feared worsening of velopharyngeal insufficiency after the procedure. This review aims at collecting the available evidence on this subject, to frame possible further areas of research and interventions. METHODS: A PRISMA-compliant systematic review was performed. Multiple databases were searched with criteria designed to include all studies focusing on the role of adenoidectomy in treating middle ear disease in cleft palate children. After duplicate removal, abstract and full-text selection, and quality assessment, we reviewed eligible articles for clinical indications and outcomes. RESULTS: Among 321 unique citations, 3 studies published between 1964 and 1972 (2 case series and a retrospective cohort study) were deemed eligible, with 136 treated patients. The outcomes were positive in all three articles in terms of conductive hearing loss improvement, recurrent otitis media episodes reduction, and effusive otitis media resolution. CONCLUSION: Despite promising results, research on adenoidectomy in treating middle ear disease in the cleft population has stopped in the mid-Seventies. No data are, therefore, available on the role of modern conservative adenoidectomy techniques (endoscopic and/or partial) in this context. Prospective studies are required to define the role of adenoidectomy in cleft children, most interestingly in specific subgroups such as patients requiring re-tympanostomy, given their known risk of otologic sequelae.

Role of SatO2, PaO2/FiO2 Ratio and PaO2 to Predict Adverse Outcome in COVID-19: A Retrospective, Cohort Study.

COVID-19 respiratory failure is a life-threatening condition. Oxygenation targets were evaluated in a non-ICU setting. In this retrospective, observational study, we enrolled all patients admitted to the University Hospital of Genoa, Italy, between 1 February and 31 May 2020 with an RT-PCR positive for SARS-CoV-2. PaO2, PaO2/FiO2 and SatO2% were collected and analyzed at time 0 and in case of admission, patients who required or not C-PAP (groups A and B) were categorized. Each measurement was correlated to adverse outcome. A total of 483 patients were enrolled, and 369 were admitted to hospital. Of these, 153 required C-PAP and 266 had an adverse outcome. Patients with PaO2 <60 and >100 had a higher rate of adverse outcome at time 0, in groups A and B (OR 2.52, 3.45, 2.01, respectively). About the PaO2/FiO2 ratio, the OR for < 300 was 3.10 at time 0, 4.01 in group A and 4.79 in group B. Similar odds were found for < 200 in any groups and < 100 except for group B (OR 11.57). SatO2 < 94% showed OR 1.34, 3.52 and 19.12 at time 0, in groups A and B, respectively. PaO2 < 60 and >100, SatO2 < 94% and PaO2/FiO2 ratio < 300 showed at least two- to three-fold correlation to adverse outcome. This may provide simple but clear targets for clinicians facing COVID-19 respiratory failure in a non ICU-setting.

Management and Outcome of Parathyroid Carcinoma-Induced Primary Hyperparathyroidism: A Single-Centre Experience.

BACKGROUND: Parathyroid carcinoma (PC) is the rarest endocrine cancer and an infrequent cause of primary hyperparathyroidism (PHPT), responsible for less than 1% of cases. Due to its rarity, treatment is challenging. METHODS: A retrospective cohort study on 462 patients referred for parathyroidectomy to Thyroid and Parathyroid Unit at Santi Paolo e Carlo Hospital, Milan, Italy, from 2011 to 2021. We identified and individually described the patients affected with PC. Then, we split all patients treated for PHPT into four groups based on the cause: PC, adenoma, atypical adenoma, and hyperplasia. Patients' demographics, preoperative evaluation results, intraoperative findings, and outcomes for the PC group were compared with groups of PHPT due to benign causes. RESULTS: Eight cases of PC were identified, five males and three females. Seven cases presented with symptoms of hypercalcemia and one with a neck mass. Five underwent en bloc resections and three local excisions. Histopathological features showed capsular invasion in four patients, capsular and soft tissue invasion in three patients, and vascular invasion in one case. No patients had distant metastasis. One patient was classed as high risk based on the Schulte classification system. All patients treated for PC were alive and disease-free at a mean follow-up of 38.4 months. When compared with other PHPT patients, PC patients were more frequently male and had higher preoperative blood calcium and PTH and lower phosphate levels, larger and heavier parathyroids excised, lower postoperative calcium, and a higher rate of postoperative hypoparathyroidism. CONCLUSION: Our study highlights some aspects valuable to suspect PC and differentiate PHPT-PC from benign causes of PHPT preoperatively. Preoperative suspicion of malignancy is essential to guarantee the best course of treatment for patients. Although limited for size and follow-up, the excellent outcome of our series seems to support the value of both surgery extension and risk class according to the Schulte classification as possible prognostic factors for recurrence.

Evaluation of Wisconsin and CaPTHUS Indices Usefulness for Predicting Monoglandular and Multiglandular Disease in Patients with Primary Hyperparathyroidism through the Analysis of a Single-Center Experience.

BACKGROUND: The main challenge for treating primary hyperparathyroidism (PHPT) is to understand if it is caused by a single adenoma (80-85% of the cases) or by a multiglandular disease (15-20%), both preoperatively and intraoperatively. For this reason, some preoperative scores were proposed in the literature, to perform focused parathyroidectomy, avoiding intraoperative parathormone assay (ioPTH). The most known are the CaPTHUS test and the Wisconsin index. We applied them to our experience. METHODS: A retrospective cohort study on 462 patients referred for parathyroidectomy to Thyroid and Parathyroid Unit at Santi Paolo e Carlo Hospital, Milan, Italy, from 2011 to 2021. Only patients affected with benign PHPT and neck ultrasound performed at our institution were included. Both patients for whom preoperative imaging agreed with the localization of a single diseased parathyroid and those with only ultrasound or scintigraphy positive for parathyroid localization underwent Mini-Invasive Video-assisted parathyroidectomy. In all cases, ioPTH assay was performed. The conversion to bilateral neck exploration was decided based on the drop in ioPTH. CaPTHUS score and the Wisconsin index (Win) were applied to the series. CaPTHUS score ≥3 and Win index >1600, according to the original studies of the literature, were considered at high probability of monoglandular disease. Outcomes in these two groups were examined. RESULTS: 236 patients were eligible for the study. The pathology resulted in multiglandular disease in 24 patients (10.2%). Among these, 18 (75.0%) obtained a CaPTHUS score ≥3, and 20 (83.3%) had a Win index>1600. Intraoperative PTH allowed to identify multiglandular disease in 16 of 18 cases with CaPTHUS ≥3 and in 18 of 20 cases with win >1600, who could have been lost, based only on the results of these 2 tests. CONCLUSION: Based on our experience, CaPTHUS test and Wisconsin index were not so useful in predicting multiglandular disease as ioPTH.

Through The Back Door: Expiratory Accumulation of SARS-Cov-2 in the Olfactory Mucosa as Mechanism for CNS Penetration.

Introduction: SARS-CoV-2 is a respiratory virus supposed to enter the organism through aerosol or fomite transmission to the nose, eyes and oropharynx. It is responsible for various clinical symptoms, including hyposmia and other neurological ones. Current literature suggests the olfactory mucosa as a port of entry to the CNS, but how the virus reaches the olfactory groove is still unknown. Because the first neurological symptoms of invasion (hyposmia) do not correspond to first signs of infection, the hypothesis of direct contact through airborne droplets during primary infection and therefore during inspiration is not plausible. The aim of this study is to evaluate if a secondary spread to the olfactory groove in a retrograde manner during expiration could be more probable. Methods: Four three-dimensional virtual models were obtained from actual CT scans and used to simulate expiratory droplets. The volume mesh consists of 25 million of cells, the simulated condition is a steady expiration, driving a flow rate of 270 ml/s, for a duration of 0.6 seconds. The droplet diameter is of 5 µm. Results: The analysis of the simulations shows the virus to have a high probability to be deployed in the rhinopharynx, on the tail of medium and upper turbinates. The possibility for droplets to access the olfactory mucosa during the expiratory phase is lower than other nasal areas, but consistent. Discussion: The data obtained from these simulations demonstrates the virus can be deployed in the olfactory groove during expiration. Even if the total amount in a single act is scarce, it must be considered it is repeated tens of thousands of times a day, and the source of contamination continuously acts on a timescale of several days. The present results also imply CNS penetration of SARS-CoV-2 through olfactory mucosa might be considered a complication and, consequently, prevention strategies should be considered in diseased patients.

Isolated olfactory cleft involvement in SARS-CoV-2 infection: prevalence and clinical correlates.

PURPOSE: Smell alterations are a symptom of COVID-19 and have been associated with olfactory cleft mucosal thickening (OCMT). Although their pathogenesis is unclear, evidences link them to viral neuroinvasive potential. This study aims at estimating the prevalence of OCMT in CT scans of COVID-19 patients and investigating its clinical correlates. METHODS: In a single-institution retrospective cross-sectional study, we included all patients hospitalized for COVID-19 undergoing head CT scan for any reason. Exclusion criteria were history of recent head trauma or chronic rhinosinusitis; opacification > 2 mm in any sinonasal space other than the olfactory cleft; CT performed during/after invasive ventilation or feeding via nasogastric tube. We recorded the prevalence of OCMT and related it to age, sex, need for invasive ventilation during hospital stay, outcome, length of hospital stay, diffusion of lung SARS-CoV-19 lesions and outcome. RESULTS: 63 eligible patients were identified (39 male, 24 female; median age 77.82 ± 17.77 years). OCMT was identified in 16 patients (25.4%; 95% CI 15.3-37.9%). Patients with OCMT had longer hospital stays (median 16 ± 4 vs. 9 ± 14.5 days, p = .009, Mann-Whitney U test) and required invasive ventilation more frequently than patients without mucosal thickening (OR 4.89, 95% CI 0.96-24.89, p = .063, Fisher's test). No other difference was observed. CONCLUSION: OCMT affects nearly one in four patients hospitalized for COVID-19. It is associated with a worse disease course irrespective of age, sex and diffusion of lung lesions, although with no direct effect on survival.

Pharyngolaryngeal spasm-induced dysphagia in an epileptic patient undergoing vagus nerve stimulation therapy.

Vagus nerve stimulation for refractory epilepsy may induce laryngeal side effects such as dysphonia and dysphagia. Careful tuning of the stimulation parameters and collaboration between epileptologists and otolaryngologists can help significantly reduce side effects.

Unusual solution to abdominal pain with contrast enhanced ultrasound.

Splenic infarction might be the symptom onset of an important underlying disease. The possibility of splenic infarction must be inserted into differential diagnosis in all those patients who have pain in the upper left quadrant and/or on the left flank. When faced with a case of splenic infarction in a patient who has flown or climbed to high altitudes, it is appropriate to consider the possibility of an haemoglobinopathy. The diagnosis is far from being obvious for emergency physicians. For these reasons, it is very important to proceed as a multidisciplinary team with appropriate diagnostic examinations. The European Guidelines for non-hepatic applications of contrast enhanced ultrasound suggest the usage of this tool for investigation of suspected ischaemic lesions of the spleen.

Clonal mast cell disorders in patients with systemic reactions to Hymenoptera stings and increased serum tryptase levels.

BACKGROUND: Anaphylaxis after Hymenoptera stings has been reported in subjects with mastocytosis, but few data exist regarding disease prevalence in populations allergic to these insects. OBJECTIVE: The incidence of clonal mast cell (MC) disorders in subjects with both systemic reactions to Hymenoptera stings and increased serum baseline tryptase (sBT) levels was assessed by using bone marrow (BM) aspirates and biopsy specimens. METHODS: Subjects with a history of a systemic reaction caused by a Hymenoptera sting underwent the standard diagnostic work-up for Hymenoptera allergy, and sBT levels were measured. Subjects with an increased sBT level had BM evaluation that included histology/cytology, flow cytometry, and detection of KIT mutations. RESULTS: Forty-four (11.6%) of 379 subjects with systemic reactions had increased sBT levels (>11.4 ng/mL), and 31 (70.5%) of these had a history of anaphylaxis. Thirty-four subjects with increased sBT levels underwent a BM analysis. Histology detected diagnostic or subdiagnostic MC infiltrates in 22 (65%) of 34 patients. Abnormal MCs were identified by means of flow cytometry and cytology in 26 (78.8%) of 33 and 20 (58.8%) of 34 subjects, respectively. A KIT mutation was detected in 17 (54.8%) of 31 subjects. The diagnosis was indolent systemic mastocytosis in 21 (61.7%) of 34 subjects and monoclonal MC activation syndrome in 9 (26.5%) of 34 subjects. All subjects with anaphylaxis had one of those 2 disorders. CONCLUSION: The concomitant presence of systemic reactions (especially anaphylaxis) after Hymenoptera stings and increased sBT levels strongly suggests that a BM examination is indicated for the diagnosis of clonal MC disease.