Comparison of Adverse Effects of Two SARS-CoV-2 Vaccines Administered in Workers of the University of Padova.

Introduction: In Italy, on December 2020, workers in the education sector were identified as a priority population to be vaccinated against COVID-19. The first authorised vaccines were the Pfizer-BioNTech mRNA (BNT162b2) and the Oxford-AstraZeneca adenovirus vectored (ChAdOx1 nCoV-19) vaccines. Aim: To investigate the adverse effects of two SARS-CoV-2 vaccines in a real-life preventive setting at the University of Padova. Methods: Vaccination was offered to 10116 people. Vaccinated workers were asked to voluntarily report symptoms via online questionnaires sent to them 3 weeks after the first and the second shot. Results: 7482 subjects adhered to the vaccination campaign and 6681 subjects were vaccinated with ChAdOx1 nCoV-19 vaccine and 137 (fragile subjects) with the BNT162b2 vaccine. The response rate for both questionnaires was high (i.e., >75%). After the first shot, the ChAdOx1 nCoV-19 vaccine caused more fatigue (p < 0.001), headache (p < 0.001), myalgia (p < 0.001), tingles (p = 0.046), fever (p < 0.001), chills (p < 0.001), and insomnia (p = 0.016) than the BNT162b2 vaccine. After the second dose of the BNT162b2 vaccine, more myalgia (p = 0.033), tingles (p = 0.022), and shivers (p < 0.001) than the ChAdOx1 nCoV-19 vaccine were elicited. The side effects were nearly always transient. Severe adverse effects were rare and mostly reported after the first dose of the ChAdOx1 nCoV-19 vaccine. They were dyspnoea (2.3%), blurred vision (2.1%), urticaria (1.3%), and angioedema (0.4%). Conclusions: The adverse effects of both vaccines were transient and, overall, mild in severity.

Laparoscopic Heller-Dor is an effective long-term treatment for end-stage achalasia.

BACKGROUND: The end-stage achalasia is a difficult condition to treat, for the esophageal diameter and conformation of the gullet, that may progress to a sigmoid shape. The aim of this study was to examine the outcome of Laparoscopic Heller-Dor in patients with end-stage achalasia, comparing them with patients who had mega-esophagus without a sigmoid shape. METHODS: From 1992 to 2020, patients with a diagnosis of sigmoid esophagus, or radiological stage IV achalasia (the SE group), and patients with a straight esophagus larger than 6 cm in diameter, or radiological stage III achalasia (the NSE group), were all treated with LHD. The two groups were compared in terms of patients' symptoms, based on the Eckardt score, and on barium swallow, endoscopy and manometry performed before and after the treatment. The failure of the treatment was defined as an Eckardt score > 3, or the need for further treatment. RESULTS: The study involved 164 patients: 73 in the SE group and 91 in the NSE group. No intra- or postoperative mortality was recorded. The median follow-up was 51 months (IQR 25-107). The outcome was satisfactory in 71.2% of patients in the SE group, and in 89% of those in the NSE group (p = 0.005). CONCLUSIONS: SE is certainly the worst condition of the disease and the final outcome of LHD, in term of symptom control, is inferior compared to NSE. Despite this, almost 3/4 of the SE patients experienced a significant relieve in symptoms after LHD, which may therefore still be the first surgical option to offer to these patients, before considering esophagectomy.

Multimodal treatment of radiation-induced esophageal cancer: Results of a case-matched comparative study from a single center.

PURPOSE: Radiation-induced esophageal cancer (RIEC) is a rare but severe late consequence of radiotherapy. The literature regarding this topic is predominately limited in describing the risk of this disease. Tumor behavior, treatment strategies, and prognosis of this cancer remain poorly defined. PATIENTS AND METHODS: We collected data of patients who were referred to our unit between 2000 and 2020 for RIEC. After tumor board discussion, upfront surgery or neoadjuvant therapy and surgery were indicated as the main treatment. Preoperative characteristics, long-term and short-term postoperative outcomes of RIEC patients were compared with a 1:1 clustering-matched cohort of patients affected by primary esophageal cancer (PEC). RESULTS: At pre-matching, 54 RIEC and 936 PEC patients were enrolled. The median time between primary irradiation and diagnosis of RIEC was 13.5 years, and the median primary radiation dose was 60 Gy. Compared to the unmatched cohort of PECs, RIEC patients were more frequently female (p = 0.0007), had earlier detection of disease (p = 0.03) and presented more frequently with upper esophageal cancers (p < 0.0001). Neoadjuvant treatment was used less frequently in RIEC patients (p < 0.0001). After matching, the 51 RIEC and 50 PEC patients showed comparable results in terms of exposure to neoadjuvant treatment, surgical radicality and survival outcomes. RIEC patients had more severe postoperative complications (p = 0.04) and a higher proportion of pulmonary complications (p = 0.04). CONCLUSIONS: Curative treatments are feasible for RIEC. Neoadjuvant chemotherapy or chemoradiation can be used in this subgroup, treatment response and long-term outcomes are comparable to those of PEC. The risk of postoperative complications is probably related to the detrimental effect of primary irradiation on lung function.

Could the Pittsburgh Severity Score guide the treatment of esophageal perforation? Experience of a single referral center.

BACKGROUND: Esophageal perforation (EP) is characterized by high morbidity and mortality. The Pittsburgh Severity Score (PSS) is a scoring system based on clinical factors at the time of EP presentation, intended to guide treatment. The aim of the study is to verify PSS usefulness in stratifying EP severity and in guiding clinical decisions. METHODS: All patients referred to our unit for EP between January 2005 and January 2020 were enrolled. Patients were stratified according to their PSS into three groups (PSS ≤ 2, 3-5, and >5): the postoperative outcomes were compared. The predictive value of the PSS was evaluated by simple linear and logistic regression for the following outcomes: need for surgery, complications, in-hospital mortality, intensive care unit (ICU) and hospital stay, time to refeeding, and need for reintervention. RESULTS: Seventy-three patients were referred for EP (male/female, 46/27). Perforations were more frequently iatrogenic (41.1%) or spontaneous (38.3%). The median PSS was 4 (interquartile range, 2-6). Surgery was required in 60.3% of cases. Pittsburgh Severity Score was associated with ICU admission, hospital stay, need for surgery and reintervention, postperforation complications and mortality. After regression analysis, PSS was significantly predictive of postperforation complications (p < 0.01), in-hospital mortality (p = 0.01), ICU admission (p < 0.01), need for surgical treatment (p < 0.01), and need for reintervention (p = 0.02). CONCLUSION: Pittsburgh Severity Score is useful in stratifying patients in risk groups with different morbidity and mortality. It is also useful in guiding the therapeutic conduct, selecting patients for nonoperative management. Prospective studies are needed to confirm the role of the PSS in the treatment of esophageal perforation. LEVEL OF EVIDENCE: Management, Therapeutic/Care; level IV.

Pharyngo-Esophageal Perforation Following Anterior Cervical Spine Surgery: A Single Center Experience and a Systematic Review of the Literature.

STUDY DESIGN: Case series and systematic review of the Literature. OBJECTIVES: Pharyngo-esophageal perforation (PEP) is a rare, life-threatening complication of anterior cervical spine surgery (ACSS). Best management of these patients remains poorly defined. The aim of this study is to present our experience with this entity and to perform a systematic Literature review to better clarify the appropriate treatment of these patients. METHODS: Patients referred to our center for PEP following ACSS (January 2002-December 2018) were identified from our database. Moreover, an extensive review of the English Literature was conducted according to the 2009 PRISMA guidelines. RESULTS: Twelve patients were referred to our Institution for PEP following ACSS. Indications for ACSS were trauma (n = 10), vertebral metastases (n = 1) and disc herniation (n = 1). All patients underwent hardware placement at the time of ACSS. There were 6 early and 6 delayed PEP. Surgical treatment was performed in 11 patients with total or partial removal of spine fixation devices, autologous bone graft insertion or plate/cage replacement, anatomical suture of the fistula and suture line reinforcement with myoplasty. Complete resolution of PEP was observed in 6 patients. Five patients experienced PEP persistence, requiring further surgical management in 2 cases. At a median follow-up of 18.8 months, all patients exhibited permanent resolution of the perforation. CONCLUSIONS: PEP following ACSS is a rare but dreadful complication. Partial or total removal of the fixation devices, direct suture of the esophageal defect and coverage with tissue flaps seems to be an effective surgical approach in these patients.

Association of CLDN18 Protein Expression with Clinicopathological Features and Prognosis in Advanced Gastric and Gastroesophageal Junction Adenocarcinomas.

The tight junction protein claudin-18 (CLDN18), is often expressed in various cancer types including gastric (GC) and gastroesophageal adenocarcinomas (GECs). In the last years, the isoform CLDN18.2 emerged as a potential drug target in metastatic GCs, leading to the development of monoclonal antibodies against this protein. CLDN18.2 is the dominant isoform of CLDN18 in normal gastric and gastric cancer tissues. In this work, we evaluated the immunohistochemical (IHC) profile of CLDN18 and its correlation with clinical and histopathological features including p53, E-cadherin, MSH2, MSH6, MLH1, PMS2, HER2, EBER and PD-L1 combined positive score, in a large real-world and mono-institutional series of advanced GCs (n = 280) and GECs (n = 70). The association of IHC results with survival outcomes was also investigated. High membranous CLDN18 expression (2+ and 3+ intensity ≥75%) was found in 117/350 (33.4%) samples analyzed. CLDN18 expression correlated with age <70 (p = 0.0035), positive EBV status (p = 0.002), high stage (III, IV) at diagnosis (p = 0.003), peritoneal involvement (p < 0.001) and lower incidence of liver metastases (p = 0.013). CLDN18 did not correlate with overall survival. The predictive value of response of CLDN18 to targeted agents is under investigation in several clinical trials and further studies will be needed to select patients who could benefit from these therapies.

The ERG1A K+ Channel Is More Abundant in Rectus abdominis Muscle from Cancer Patients Than that from Healthy Humans.

BACKGROUND: The potassium channel encoded by the ether-a-gogo-related gene 1A (erg1a) has been detected in the atrophying skeletal muscle of mice experiencing either muscle disuse or cancer cachexia and further evidenced to contribute to muscle deterioration by enhancing ubiquitin proteolysis; however, to our knowledge, ERG1A has not been reported in human skeletal muscle. METHODS AND RESULTS: Here, using immunohistochemistry, we detect ERG1A immunofluorescence in human Rectus abdominis skeletal muscle sarcolemma. Further, using single point brightness data, we report the detection of ERG1A immunofluorescence at low levels in the Rectus abdominis muscle sarcolemma of young adult humans and show that it trends toward greater levels (10.6%) in healthy aged adults. Interestingly, we detect ERG1A immunofluorescence at a statistically greater level (53.6%; p < 0.05) in the skeletal muscle of older cancer patients than in age-matched healthy adults. Importantly, using immunoblot, we reveal that lower mass ERG1A protein is 61.5% (p < 0.05) more abundant in the skeletal muscle of cachectic older adults than in healthy age-matched controls. Additionally, we report that the ERG1A protein is detected in a cultured human rhabdomyosarcoma line that may be a good in vitro model for the study of ERG1A in muscle. CONCLUSIONS: The data demonstrate that ERG1A is detected more abundantly in the atrophied skeletal muscle of cancer patients, suggesting it may be related to muscle loss in humans as it has been shown to be in mice experiencing muscle atrophy as a result of malignant tumors.

Perturbed BMP signaling and denervation promote muscle wasting in cancer cachexia.

Most patients with advanced solid cancers exhibit features of cachexia, a debilitating syndrome characterized by progressive loss of skeletal muscle mass and strength. Because the underlying mechanisms of this multifactorial syndrome are incompletely defined, effective therapeutics have yet to be developed. Here, we show that diminished bone morphogenetic protein (BMP) signaling is observed early in the onset of skeletal muscle wasting associated with cancer cachexia in mouse models and in patients with cancer. Cancer-mediated factors including Activin A and IL-6 trigger the expression of the BMP inhibitor Noggin in muscle, which blocks the actions of BMPs on muscle fibers and motor nerves, subsequently causing disruption of the neuromuscular junction (NMJ), denervation, and muscle wasting. Increasing BMP signaling in the muscles of tumor-bearing mice by gene delivery or pharmacological means can prevent muscle wasting and preserve measures of NMJ function. The data identify perturbed BMP signaling and denervation of muscle fibers as important pathogenic mechanisms of muscle wasting associated with tumor growth. Collectively, these findings present interventions that promote BMP-mediated signaling as an attractive strategy to counteract the loss of functional musculature in patients with cancer.

Forensic Implications of Anatomical Education and Surgical Training With Cadavers.

Anatomical education and surgical training with cadavers are usually considered an appropriate method of teaching, above all for all surgeons at various levels. Indeed, in such a way they put into practice and exercise a procedure before performing it live, reducing the learning curve in a safe environment and the risks for the patients. Really, up to now it is not clear if the nonuse of the cadavers for anatomical education and surgical training can have also forensic implications. A substantial literature research was used for this review, based on PubMed and Web of Science database. From this review, it is clear that the cadaveric training could be considered mandatory, both for surgeons and for medical students, leading to a series of questions with forensic implications. Indeed, there are many evidences that a cadaver lab can improve the learning curve of a surgeon, above all in the first part of the curve, in which frequent and severe complications are possible. Consequently, a medical responsibility for residents and surgeons which perform a procedure without adequate training could be advised, but also for hospital, that has to guarantee a sufficient training for its surgeons and other specialists through cadaver labs. Surely, this type of training could help to improve the practical skills of surgeons working in small hospitals, where some procedures are rare. Cadaver studies can permit a better evaluation of safety and efficacy of new surgical devices by surgeons, avoiding using patients as ≪guinea pigs≫. Indeed, a legal responsibility for a surgeon and other specialists could exist in the use of a new device without an apparent regulatory oversight. For a good medical practice, the surgeons should communicate to the patient the unsure procedural risks, making sure the patients' full understanding about the novelty of the procedure and that they have used this technique on few, if any, patients before. Cadaver training could represent a shortcut in the standard training process, increasing both the surgeon learning curve and patient confidence. Forensic clinical anatomy can supervise and support all these aspects of the formation and of the use of cadaver training.

The Prognostic Value of Low Muscle Mass in Pancreatic Cancer Patients: A Systematic Review and Meta-Analysis.

Low muscle mass is associated with reduced survival in patients with different cancer types. The interest in preoperative sarcopenia and pancreatic cancer has risen in the last decade as muscle mass loss seems to be associated with poorer survival, higher postoperative morbidity, and mortality. The aim of the present study was to review the literature to compare the impact of low muscle mass on the outcomes of patients undergoing surgery for pancreatic adenocarcinoma. An extensive literature review was conducted according to the 2009 Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and 10 articles were analyzed in detail and included in the meta-analysis. Data were retrieved on 2811 patients undergoing surgery for pancreatic cancer. Meta-analysis identified that patients with low muscle mass demonstrated a significantly reduced OS when compared to patients without alterations of the muscle mass (ROM 0.86; 95% CI: 0.81-0.91, p < 0.001), resulting in a 14% loss for the former. Meta-analysis failed to identify an increase in the postoperative complications and length of stay of patients with low muscle mass. Our analysis confirms the role of low muscle mass in influencing oncologic outcomes in pancreatic cancer. Its role on surgical outcomes remains to be established.

Optimal Treatment of cT2N0 Esophageal Carcinoma: Is Upfront Surgery Really the Way?

BACKGROUND: Staging is inaccurate for cT2N0 esophageal cancer, and patients often are clinically mis-staged. This study aimed to evaluate the outcome after upfront surgery or neoadjuvant therapy, considering the impact of clinical "mis-staging." METHODS: This study reviewed patients with squamous cell carcinoma (SCC) or adenocarcinoma (ADK) of the esophagus who underwent upfront surgery (S group) or neoadjuvant treatment (chemoradiotherapy [CRT] group) for cT2N0 cancer. Overall survival (OS), disease-free survival (DFS), morbidity, and mortality were evaluated. Correctly staged (cTNM = pTNM), understaged (cTNM < pTNM), and overstaged (cTNM > pTNM) patients in the S group and the CRT group were analyzed. Risk factors for unexpected lymph-node involvement were identified in the S group and for cancer-related death in the whole study cohort. RESULTS: The study enrolled 229 patients with cT2N0 esophageal cancer. The 5-year OS rate was 34.2% in the S group versus 55.7% in the CRT group (p = 0.0088). The DFS also was significantly higher (p = 0.01). The morbidity and mortality rates were similar. In the S group, the cTNM was correctly staged for 21.4% and understaged for 63.4% of the patients, with 48.7% of the patients showing unexpected nodal involvement. A tumor length of 3 cm or more was an independent predictor of nodal metastases in SCC (p = 0.03), as was lymphovascular invasion (LVI) in ADK (p < 0.01). Cancer-related mortality was independently associated with lymph-node metastases (p = 0.03) and treatment by upfront surgery (p = 0.01). CONCLUSION: Given the high rate of understaged patients in this study (63.4%), the authors advocate for combining the induction therapy with surgery in cT2N0, achieving better survival with similar morbidity and mortality.

Laparoscopic Revisional Surgery After Failed Heller Myotomy for Esophageal Achalasia: Long-Term Outcome at a Single Tertiary Center.

BACKGROUND: Laparoscopic Heller myotomy (HM) has gained acceptance as the gold standard of treatment for achalasia. However, 10-20% of the patients will experience symptom recurrence, thus requiring further treatment including pneumodilations (PD) or revisional surgery. The aim of our study was to assess the long-term outcome of laparoscopic redo HM. METHODS: Patients who underwent redo HM at our center between 2000 and 2019 were enrolled. Postoperative outcomes of redo HM patients (redo group) were compared with that of patients who underwent primary laparoscopic HM in the same time span (control group). For the control group, we randomly selected patients matched for age, sex, FU time, Eckardt score (ES), previous PD, and radiological stage. Failure was defined as an Eckardt score > 3 or the need for re-treatment. RESULTS: Forty-nine patients underwent laparoscopic redo HM after failed primary HM. A new myotomy on the right lateral wall of the EGJ was the procedure of choice in the majority of patients (83.7%). In 36 patients (73.5%) an anti-reflux procedure was deemed necessary. Postoperative outcomes were somewhat less satisfactory, albeit comparable to the control group; the incidence of postoperative GERD was higher in the redo group (p < 0.01). At a median 5-year FU time, a good outcome was obtained in 71.4% of patients in the redo group; further 5 patients (10.2%) obtained a long-term symptom control after complementary PD, thus bringing the overall success rate to 81.6%. Stage IV disease at presentation was independently associated with a poor outcome of revisional LHD (p = 0.003). CONCLUSIONS: This study reports the largest case series of laparoscopic redo HM to date. The procedure, albeit difficult, is safe and effective in relieving symptoms in this group of patients with a highly refractory disease. The failure rate, albeit not significantly, and the post-operative reflux are higher than after primary HM. Patients with stage IV disease are at high risk of esophagectomy.

Laparoscopic Heller-Dor Is an Effective Treatment for Esophageal-Gastric Junction Outflow Obstruction.

BACKGROUND: The treatment of esophagogastric junction outflow obstruction (EGJOO) currently mirrors that of achalasia, but this is based on only a few studies on small case series. The aim of this prospective, controlled study was to assess the outcome of laparoscopic Heller-Dor (LHD) in patients with EGJOO, as compared with patients with esophageal achalasia. MATERIALS AND METHODS: Between 2016 and 2019, patients with manometric diagnosis of idiopathic EGJOO and patients with radiological stage I achalasia, both treated with LHD, were compared. The achalasia group was further analyzed by subgrouping the patients based on the manometric pattern. Treatment failure was defined as the persistence or reoccurrence of an Eckardt score > 3 or the need for retreatment. RESULTS: During the study period, 150 patients were enrolled: 25 patients had EGJOO and 125 had radiological stage I achalasia (25 pattern I, 74 pattern II, and 26 pattern III). The median follow-up was 24 months (IQR: 34-16). Treatment was successful in 96% of patients in the EGJOO group and in 96% of achalasia patients with pattern I, 98.7% in those with pattern II, and 96.2% of those with pattern III (p=0.50). High-resolution manometry showed a reduction in the LES resting pressure and integrated relaxation pressure for all patients in all 4 groups (p<0.001). CONCLUSION: This is the first comparative study based on prospective data collection to assess the outcome of LHD in patients with EGJOO. LHD emerged as an effective treatment for EGJOO, with an excellent success rate, comparable with the procedure's efficacy in treating early-stage achalasia.

Does Pathological Stage and Nodal Involvement Influence Long Term Oncological Outcomes after CROSS Regimen for Adenocarcinoma of the Esophagogastric Junction? A Multicenter Retrospective Analysis.

Background:After the results reported by the "Chemoradiotherapy for esophageal Cancer Followed by Surgery Study" (CROSS) trial, neo-adjuvant chemoradiotherapy became the standard treatment for locally advanced cancers of esophagus and gastroesophageal junction (GEJ). Excellent results were reported for squamocellular carcinomas (SCCs). Since the advent of the CROSS regimen, the results of surgery for esophageal adenocarcinomas (EAC) have cast some doubts about its efficacy on overall survival (OS) even in the presence of local response. This study evaluated the relation between pathological (yp) stage after CROSS regimen followed by surgery for adenocarcinoma of cardia and overall (OS) and disease-free survival (DFS). Sites of relapse after surgery were also analyzed. Methods: Patients submitted to the CROSS regimen for locally advanced EAC of the cardia followed by transthoracic esophagectomy were analyzed. Actuarial OS and DFS were analyzed and stratified according to yp stage. The site of relapse, distal and local, was also analyzed. Results: The study included 132 patients. The 50-month OS and DFS were 45% and 6.7%, respectively. No differences emerged analyzing OS according to yp stage. Time to relapse was significantly longer for yp Stage I and II, and for yp N0, compared with yp N+. Recurrence occurred in 48 cases (36.3%) with a 9 months median time to relapse. Local and distal relapse were 10 (7.5%) and 38 (28.7%) cases, respectively (p ≦ 0.001). Conclusions: Pathological stage after CROSS regimen does not relate to OS and DFS. Time to recurrence is significantly longer for yp Stages I and II and ypN0. Chemoradiotherapy in a neoadjuvant setting may influence the site of relapse, significantly reducing local recurrences.

Endoscopic diode laser therapy for gastric hyperplastic polyps in cirrhotic patients.

Purpose Endoscopic polypectomy to remove gastric hyperplastic polyps in cirrhotic patients is associated to a high risk of postprocedural bleeding. The current study set out to examine the effect of diode laser therapy used to treat this type of polyps in cirrhotic patients. Methods This single-center study retrospectively examined the data of cirrhotic patients with macroscopic bleeding or anemia who underwent diode laser therapy (940 nm wave length, 30-W power setting in continuous mode) to remove histology-confirmed hyperplastic gastric polyps. Results A total of 222 polyps (mean diameter 10 ± 8 mm) were treated in 55 patients who were included in the study. No complications such as bleeding or perforations were reported. After a mean of 5 ± 4 sessions, 31 patients (56%) were completely healed. In 16 patients (29%), there was only a partial response (mean polyp reduction diameter of 64 ± 15%), while 8 (15%) patients did not respond to treatment. Statistically significant better results were noted in the patients who underwent ≥ 2 laser sessions. Hemoglobin levels and number of blood transfusions required were not statistically different after treatment. After a mean study period of 21 ± 17 months, polyp recurrences were noted in 11 patients (20%), but none of the polyps had degenerated. Conclusion Diode laser therapy was found to be a safe treatment for hyperplastic polyps in cirrhotic patients. Due to the presence of others bleeding lesions in cirrhotic patients, this treatment did not have an impact on anemia and transfusion requirements.

Impact of COVID-19 outbreak on esophageal cancer surgery in Northern Italy: lessons learned from a multicentric snapshot.

Coronavirus Disease-19 (COVID-19) outbreak has significantly burdened healthcare systems worldwide, leading to reorganization of healthcare services and reallocation of resources. The Italian Society for Study of Esophageal Diseases (SISME) conducted a national survey to evaluate changes in esophageal cancer management in a region severely struck by COVID-19 pandemic. A web-based questionnaire (26 items) was sent to 12 SISME units. Short-term outcomes of esophageal resections performed during the lockdown were compared with those achieved in the same period of 2019. Six (50%) centers had significant restrictions in their activity. However, overall number of resections did not decrease compared to 2019, while a higher rate of open esophageal resections was observed (40 vs. 21.7%; P = 0.034). Surgery was delayed in 24 (36.9%) patients in 6 (50%) centers, mostly due to shortage of anesthesiologists, and occupation of intensive care unit beds from intubated COVID-19 patients. Indications for neoadjuvant chemo (radio) therapy were extended in 14% of patients. Separate COVID-19 hospital pathways were active in 11 (91.7%) units. COVID-19 screening protocols included nasopharyngeal swab in 91.7%, chest computed tomography scan in 8.3% and selective use of lung ultrasound in 75% of units. Postoperative interstitial pneumonia occurred in 1 (1.5%) patient. Recovery from COVID-19 pandemic was characterized by screening of patients in all units, and follow-up outpatient visits in only 33% of units. This survey shows that clinical strategies differed considerably among the 12 SISME centers. Evidence-based guidelines are needed to support the surgical esophageal community and to standardize clinical practice in case of further pandemics.

Histology of the spleen in immune thrombocytopenia: clinical-pathological characterization and prognostic implications.

OBJECTIVE: Immune thrombocytopenia (ITP) is an acquired disorder, characterized by immune-mediated platelet destruction. The spleen plays a key pathogenic role in ITP and splenectomy is a valuable second-line therapy for this disease. Little is known on ITP spleen histology and response to splenectomy is unpredictable. This study aims to characterize ITP spleen histology and assess possible predictors of splenectomy outcome. METHODS: A series of 23 ITP spleens were retrospectively assessed for the following histological parameters: density of lymphoid follicles (LFs), marginal zones (MZs), T helper and cytotoxic T cells; presence of reactive germinal centers (GCs); width of perivascular T cell sheaths; and red pulp features. Clinical and histological data were matched with postsplenectomy platelet counts to assess their prognostic relevance. RESULTS: Three histological patterns were documented: a hyperplastic white pulp pattern, a non-activated white pulp pattern (lacking GCs), and a white pulp-depleted pattern. Poor surgical responses were associated with presplenectomy high-dose steroid administration, autoimmune comorbidities and low T follicular helper cell density. The combination of such parameters stratified patients into different splenectomy response groups. The removal of accessory spleens was also associated with better outcome. CONCLUSION: ITP spleens are histologically heterogeneous and clinical-pathological parameters may help predict the splenectomy outcome.

Labelled micelles for the delivery of cytotoxic Cu(II) and Ru(III) compounds in the treatment of aggressive orphan cancers: Design and biological in vitro data.

A recent study on our metal-dithiocarbamato complexes pointed out the antiproliferative properties and the druglikeness of some new patented derivatives. In this work, the best compounds have been encapsulated in micellar nanocarriers, being also carbohydrate-functionalized on their hydrophilic surface to investigate the possibility of a cancer-selective delivery. In particular, the nonionic block copolymer Pluronic® F127 (PF127) has been chemically modified with sugars and the derivatives characterized by means of NMR spectroscopy and FT-IR spectrophotometry. Then, the two selected complexes (ß-[Ru2(PipeDTC)5]Cl (PipeDTC = piperidine dithiocarbamate) and [Cu(ProOMeDTC)2] (ProOMeDTC = L-proline methyl ester dithiocarbamate)), have been loaded into the hydrophobic core of PF127 micelles and cancer-targeting counterparts. These nanoformulations have been studied for their dimensions (DLS, TEM) and stability, and tested for their cytotoxicity against aggressive human cancer cell lines. The in vitro results were paralleled with mechanistic studies through Confocal Laser Scanning Microscopy and xCELLigence analysis.

COVID-19 challenge: proactive management of a Tertiary University Hospital in Veneto Region, Italy.

BACKGROUND: The aim of this study is to describe the successful emergency plan implemented by Padova University Hospital (AOUP) during the COVID-19 pandemic. METHODS: The emergency plan included early implementation of procedures aimed at meeting the increasing demand for testing and care while ensuring safe and timely care of all patients and guaranteeing the safety of healthcare workers. RESULTS: From 21 February to 1 May 2020, there were 3,862 confirmed cases of SARS-CoV-2 infection in the Province of Padua. A total of 485 patients were hospitalized in AOUP, of which 91 were admitted to the ICU; 12 .6% of admitted patients died. The average bed occupancy rate in the ICU was 61.1% (IQR 43.6%:77.4%). Inpatient surgery and inpatient admissions were kept for 76% and 74%, respectively, compared to March 2019. A total of 123,077 swabs were performed, 19.3% of which (23,725 swabs) to screen AOUP workers. The screening of all staff showed that 137 of 7,649 (1.8%) hospital workers were positive. No healthcare worker died. DISCUSSION: AOUP strategy demonstrated effective management of the epidemic thanks to the timely implementation of emergency procedures, a well-coordinated effort shared by all hospital Departments, and their continuous adjustment to the ongoing epidemic. Timely screening of all hospital workers proved to be particularly important to defend the hospital, avoiding epidemic clusters due to unknown positive cases.