COVID-19, inflammatory response, iron homeostasis and toxicity: a prospective cohort study in the Emergency Department of Piacenza (Italy).

BACKGROUND AND AIM: Dysregulation of iron metabolism and hyper-inflammation are two key points in the pathogenesis of coronavirus disease 2019 (COVID-19). Since high hepcidin levels and low serum iron can predict COVID-19 severity and mortality, we decided to investigate iron metabolism and inflammatory response in 32 COVID-19 adult patients with a diagnosis of COVID-19 defined by a positive result of RT-PCR nasopharyngeal swab, and admitted to an Italian emergency department for acute respiratory failure at different degree. METHODS: Patients were stratified in 3 groups based on PaO2/FiO2 ratio at admission: 13 (41%) were normoxemic at rest and suffered from exertional dyspnea (group 1); 14 (44%) had a mild respiratory failure (group 2), and 5 (15%) a severe hypoxiemia (group 3). RESULTS: White blood cells were significantly higher in group 3, while lymphocytes and hemoglobin were significantly reduced. Serum iron, transferrin saturation, non-transferrin-bound iron (NTBI) and ferritin were significantly increased in group 2. All the groups showed high hepcidin levels, but in group 3 this parameter was significantly altered. It is noteworthy that in group 1 inflammatory and oxidative indices were both within the normal range. CONCLUSIONS: We are aware that our study has some limitations, the small number of enrolled patients and the short period of data collection, but few works have been performed in the Emergency Room. However, we strongly believe that our results confirm the pivotal role of both iron metabolism dysregulation and hyper-inflammatory response in the pathogenesis of tissue and organ damage in COVID-19 patients.

Laparoscopic Resection of Synchronous Liver Metastasis Involving the Left Hepatic Vein and the Common Trunk Bifurcation: A Strategy of Parenchyma-Sparing Resection with Left Sectionectomy and 4a Subsegmentectomy by Arantius Approach.

When colorectal cancer presents with liver metastasis, hepatic resection remains the most important factor in prolonging survival, and new paradigms have been proposed to augment resectability. An adequate liver remnant and vascularisation are the only limits in complex liver resection, and parenchyma-sparing surgery is a strategy for minimising the complications, preserving liver function, and allowing patients to undergo further liver resection. The laparoscopic approach represents a new challenge, especially when lesions are located in the superior or posterior part of the liver. We discuss the case of an 81-year-old patient with a single synchronous liver metastasis involving the left hepatic vein and leaning into the middle hepatic vein at the common trunk, where we performed a simultaneous laparoscopic colonic resection with a left sectionectomy extended to segment 4a. The strategic approach to the Arantius ligament by joining the left and middle hepatic vein allowed us to avoid a major liver hepatectomy, preserve the liver parenchyma, reduce complications, enhance patient recovery, and perform the entire procedure by laparoscopy. Our example suggests that the Arantius approach to the left hepatic vein and the common trunk could be a feasible approach to consider in laparoscopic surgery for lesions located in their proximity.

Advanced stage empyemas in community-acquired pneumonia: how hospital re-organization during the Covid-19 pandemic affected the increase in surgically treated cases.

The cause of pleural empyema is bacterial pneumonia and three stages has been described in the evolution of this disease: exudative, fibrino-purulent and organizational phases. The first therapeutic intervention is the antibiotic therapy; where pharmacological therapy alone is not sufficient to eradicate the infection, it is also necessary a surgical treatment. Since the province of Piacenza having been in the epicenter area during the first Sars-Cov 2 pandemic wave in March 2020 and the number of patients with Covid-related pneumonia required invasive and non-invasive respiratory support, had a considerable organizational impact on pulmonology and respiratory unit, hindering an optimal treatment of the bacterial pneumonia both in community as well as in the hospital. Among the many "collateral" damages of the epidemiological wave of the infection with Sars Cov-2, we have been able to observe in our Hospital, also an increase of pulmonary empyemas diagnosed at an advanced stage for what we believe to be organizational and social causes directly related to the pandemic: in order to cope with the emergency the Unit of Pneumology has been since March nearly uninterruptedly dedicated to the exclusive treatment of covid patients so the pneumologist has been removed due to the need from outpatient and residential management of general pneumology.

The epidemiology of proximal femur fractures during COVID-19 emergency in Italy: a multicentric study.

BACKGROUND AND AIM: After the first Italian case of Covid-19, the Government imposed the complete closure of all areas involved by the spread of the virus to contain transmissions. There was a massive reorganization of Hospitals, a stop of all elective activities and a convertion of many hospitals in "Covid Centers''. AITOG (Associazione Italiana Traumatologia e Ortopedia Geriatrica) conducted a retrospective study on all proximal femur fractures surgeries that occurred in this period, to find out whether the pandemic and the correlated lockdown somehow changed the incidence of these events.  Methods: 10 Italian orthopedic centers were involved in the study. Considering the geographic location, three groups were created (North, Centre and South). The considered period is the Italian "Phase 1" (February 23rd - May 3rd 2020). RESULTS: the cohort is composed of 412 patients, 116 male and 296 female (mean age 81.1 ± 9.1 years). The same period of 2019 has been used as control group, with 558 patients, 156 male and 402 female (mean age 84.2 ± 8.0 years). In 2020 we counted 323 (78.4%) fractures occurred at home, 61 (14.8%) in retirement houses and 28 (6.8%) in different locations. We mainly treated fractures with intramedullary nails (n.237 57.5%). Among all patients we had 46 (11.1%) Covid-19 positive. The mortality rate within 30 days was of 51 patients (12.4%); 23 of these died because of complications related to Covid-19 while 31 of  these were in treatment with anticoagulant/antiaggregant. CONCLUSIONS: AITOG analysis demonstrates a decrease in surgical interventions for proximal femur fractures from 2019 to 2020, a reduction in patients mean age and an increase in trauma occurred in domestic environment. We also registered a consistent difference between the North, Center and South of the Country.

Serum ferritin levels in inflammation: a retrospective comparative analysis between COVID-19 and emergency surgical non-COVID-19 patients.

BACKGROUND: SARS-CoV-2 infection has spread worldwide, and the pathogenic mechanism is still under investigation. The presence of a huge inflammatory response, defined as "cytokine storm," is being studied in order to understand what might be the prognostic factors implicated in the progression of the infection, with ferritin being one of such markers. The role of ferritin as a marker of inflammation is already known, and whether it changes differently between COVID and non-COVID patients still remains unclear. The aim of this retrospective analysis is to understand whether the inflammatory process in these two types is different. METHODS: In this retrospective analysis, we compared 17 patients affected by SARS-CoV-2, who had been admitted between February and April 2020 (group A) along with 30 patients admitted for acute surgical disease with SARS-CoV-2 negative swab (group B). A further subgroup of Covid negative patients with leukocytosis was compared to group A. RESULTS: In group A, the median (interquartile range) serum ferritin was 674 (1284) ng/mL, and it was double the cutoff (300 ng/mL) in 9 out of 17 (52%). The median (IQR) value of ferritin level in the total blood samples of group B was 231, and in the subgroup with leucocytosis, 149 (145). Group A showed a significantly higher ferritin median level compared to the entire group B (two-tailed Mann-Whitney test, p < 0.0001) as well as to the subgroup with leucocytosis (p < 0.0014). CONCLUSIONS: The role of iron metabolism appears to be directly involved in COVID infection. On the other hand, in the acute inflammation of patients admitted for surgery, and probably in other common phlogistic processes, iron modifications appear to be self-limited. However, our finding suggests the use of ferritin as a marker for COVID infection.

Proximal humerus fractures in COVID-19 lockdown: the experience of three orthopedics and traumatology departments in the first ten weeks of the Italian epidemic.

INTRODUCTION: Coronavirus disease (CoVID-19) is causing millions of deaths worldwide and the crisis of the global healthcare system.  Aim Of The Study: evaluate the preliminary impact of CoVID-19 in three Italian Orthopedics and Traumatology Departments in the first 10 weeks of the national lockdown. We focused on proximal humerus fractures, analyzing data and results in comparison with the same period of 2019. MATERIALS AND METHODS: From February 22nd to May 3rd 2020, 55 patients were admitted to our departments for promixal humerus fractures. Our cohort of patients is composed by 13 males (23.6%) and 42 females (76.4%), with an average age of 73.8 ± 11.7 years (range 44 - 94). Trauma occurred at home in 43 cases (78.2%), by the roadside in 10 cases (18.2%), in a retirement home in 1 case (1.8%), and at work in 1 case (1.8%). We proposed surgical treatment in 15/55 cases, but 4 patients refused hospitalization, mainly because of the risk of contracting n-CoV19 infection. RESULTS: We noticed a decrease in proximal humerus fractures compared to 2019 (-37.5%). Particularly, we observed a significant drop in traumas occurred on the road and at work respectively 23.9% and 3.4%% in 2019, and 18.2% and 1.8% in 2020, probably due to the consequences of the national lockdown. Sports traumas had a reset during the pandemic (6 cases in 2019, 0 in 2020). As consequence, surgical treatment had a decrease due to the reduction in number of fractures, indications and patient's consent. CONCLUSION: The incidence of proximal humerus fractures had a significant reduction during CoVID-19 spread. We assume that the reasons of this reduction are to be found in the national lockdown (since March 10th, 2020) and Ministerial Decrees that limited the access to the E.R. only in case of severe traumas in order to avoid CoVID-19 spread.

The impact of COVID-19 pandemic on the Emergency Room and Orthopedic Departments in Piacenza: a retrospective analysis.

INTRODUCTION AND AIM: The Coronavirus pandemic represents one of the most massive health emergencies in the last century. Aim of the study is to evaluate the trend of E.R. accesses and orthopaedic events during the pandemic of Covid-19. MATERIALS AND METHODS: we retrospectively analysed all data related to patients admitted to the E.R. Department of the Hospital of Piacenza from August 26th 2019 to August 23rd 2020, splitting this period on February 23rd 2020. RESULTS: Our analysis shows a reduction of -18.0% in E.R. accesses. We calculated a growth of deaths in the E.R. equal to +220%. Our orthopaedic pathway recorded a drop of -26.8%. Traumas occurred at home increased (+19.1%). We note an actual drop only on proximal femur fractures (weighted average of -17.7%), while all the others underwent an increase. DISCUSSION: The amount of E.R. accesses registered a drop -18.0%, while the pathway dedicated to emergency cases underwent an increase. The major complexity of clinical conditions influenced the number of hospitalizations and the fear of the infection increased hospitalization refusals. There has been a zeroing of school traumas, a reduction in sport, transfer home-work/work-home, work, roadside, injuries. Total amount of fractures strongly increase after the end of the lockdown. CONCLUSION: our data confirmed the decrease of retirement houses, sports, works and roadsides traumas and a zeroing of schools ones, while those occurred inside domestic environment underwent a consistent raise. We noticed a reduction in femur fractures and significant spread of all fractures after the end of the lockdown.

Iron overload and Hepcidin overexpression could play a key role in COVID infection, and may explain vulnerability in elderly, diabetics, and obese patients.

BACKGROUND: The COVID epidemic hit like a tsunami worldwide. At the time of its arrival in Italy, available literary data were meager, and most of them concerned its epidemiology. World Health Organization proposed guidelines in march 2020, a strategy of treatment has been developed, and a significant number of subsequent articles have been published to understand, prevent, and cure COVID patients. METHODS: From the observation of two patients, we performed a careful analysis of scientific literature to unearth the relation between COVID infection, clinical manifestations as pneumonia and thrombosis, and to find out why it frequently affects obese, diabetics, and elderly patients. RESULTS: The analysis shows that hepcidin could represent one of such correlating factors. Hepcidin is most elevated in older age, in non-insulin diabetics patients and in obese people. It is the final target therapy of many medicaments frequently used. Viral disease, and in particular SARS-CoV19, could induce activation of the hepcidin pathway, which in turn is responsible for an increase in the iron load. Excess of iron can lead to cell death by ferroptosis and release into the bloodstream, such as free iron, which in turn has toxic and pro-coagulative effects. CONCLUSIONS: Overexpression of hepcidin and iron overload might play a crucial role in COVID infection, becoming potential targets for treatment. Hepcidin could also be considered as a biomarker to measure the effectiveness of our treatments and the restoration of iron homeostasis the final intent. (www.actabiomedica.it).

The Italian Covid-19 Phase 2 in Piacenza: results of the first semester of 2020 and future prospective of new orthopedics surgical procedures.

INTRODUCTION: During the pandemic, Piacenza's Orthopedic and Traumatology Dep. firstly dealt with the emergency with the complete closure of all the elective surgical and outpatient activities.As general population, also healthcare workers were affected by Coronavirus, increasing difficulties of epidemic management.The aim of our study is to evaluate the activity trend of the first 6months of 2020 in our hospital.Data will be compared to the two semesters of 2019, in order to have two objective samples. MATERIALS AND METHODS: We retrospectively analyzed all the orthopedics surgical procedures performed at Guglielmo da Saliceto Hospital (Piacenza, Emilia Romagna, Northern Italy)between 1/1/20 and 30/06/20. 2019 semesters (1/01/20-30/6/20 and 1/07/20-31/12/20) have been used as control group to evaluate the activity trend of the first six months of 2020, compared to the two semesters of 2019. RESULTS: We noticed a significant increase of domestic and retirement houses accidents, a consistent increase in one-month mortality rate of 2020 first semester and a decrease of mean hospitalization time.About surgical procedures, we detect a drop in the total number: in the first semester of 2020 we performed 499 (-39.9%) surgeries less than the first semester of 2019 and 337 (-30.9%) then the second one. Traumatology recorded a decrease of 27.6% than the first semester of 2019 (-204 surgeries) and of 26.3% than the second one (-191 surgeries).Concerning orthopedic procedures, in comparison to the first semester of 2019 we registered a reduction of 57.6% (-295 surgeries) and of 40.2% to the second semester (-146 surgeries). DISCUSSION AND CONCLUSION: Covid-19 forced a reorganization of the Italian Health System that led to a clear reduction of surgical procedures performed in the orthopedic and traumatology department.The "Phase 2" can't be consider the last step of the emergency.We surely will have to get used to live with this enemy, at least until we will find an effective cure or a vaccine.