Prone positioning in patients treated with non-invasive ventilation for COVID-19 pneumonia in an Italian emergency department.

We report the experience of prone ventilation in selected patients treated with helmet non-invasive ventilation (NIV) continuous positive airway pressure (CPAP) for acute respiratory failure in COVID-19 pneumonia. Preliminary results showed an improvement in the PaO2 value and PaO2/FiO2 ratio after 1 hour of prone ventilation. No variation of the lung ultrasound pattern before and after prone ventilation has been detected. At the time of writing, we attempted proning with helmet NIV CPAP in 10 patients. In 4 out of 10 patients, the attempt failed due to lack of compliance of the patient, scarce pain control even with ongoing treatment and refusal by the patient to prone positioning.

A multicentre observational study for early diagnosis of Gaucher disease in patients with Splenomegaly and/or Thrombocytopenia.

Gaucher disease (GD) is the most common lysosomal disorder resulting from deficient activity of the ß-glucosidase enzyme that causes accumulation of glucosylceramide in the macrophage-monocyte system. Notably, because of non-specific symptoms and a lack of awareness, patients with GD experience long diagnostic delays. The aim of this study was to apply a diagnostic algorithm to identify GD type 1 among adults subjects referred to Italian haematology outpatient units because of splenomegaly and/or thrombocytopenia and, eventually, to estimate the prevalence of GD in this selected population. One hundred and ninety-six subjects (61 females, 135 males; mean age 47.8 ± 18.2 years) have been enrolled in the study and tested for ß-glucosidase enzyme activity on dried blood spot (DBS). Seven of 196 patients have been diagnosed with GD, (5 females and 2 males) with mean age 31.8 ± 8.2 years, with a prevalence of 3.6% (with a prevalence of 3.6% (I95% CI 1.4-7.2; 1/28 patients) in this population. These results show that the use of an appropriate diagnostic algorithm and a simple diagnostic method, such as DBS, are important tools to facilitate the diagnosis of a rare disease even for not disease-expert physicians.

The role of TMPRSS6 polymorphisms in iron deficiency anemia partially responsive to oral iron treatment.

Iron refractory iron deficiency anemia (IRIDA) is a rare hereditary disease caused by mutations in TMPRSS6 gene encoding Matriptase-2, a negative regulator of hepcidin transcription. Up to now, 53 IRIDA patients from 35 families with different ethnic origins have been reported and 41 TMPRSS6 mutations have been identified. TMPRSS6 polymorphisms are more frequent than mutations, and have been associated with variation in iron and hematologic parameters. Our study evaluated their presence in 113 subjects with iron deficiency anemia (IDA) partially responsive to oral iron therapy and in 50 healthy blood donors. Thalassemic trait was diagnosed in 38 patients. Sequencing analysis of TMPRSS6 gene revealed that the frequency of several polymorphisms was markedly different between IDA subjects and controls. In particular, the V736A TMPRSS6 polymorphism was associated to moderately lower hemoglobin, mean corpuscular volume, and mean corpuscular hemoglobin levels, and in thalassemia carriers with marked anemia and microcytosis. A new variant-H448R- and two uncommon polymorphisms -A719T and V795I- were also identified. These results indicate that TMPRSS6 polymorphisms are more frequent in subjects with persistent IDA than in healthy controls, and in thalassemia carriers V736A variant may account for lower hemoglobin and MCV levels. Further studies in larger court of patients are necessary to identify potential haplotypes and polymorphisms responsible for low response to oral iron treatment and may be useful for planning a correct iron supplementation.

Myocardial and hepatic iron overload assessment by region-based and pixel-wise T2* mapping analysis: technical pitfalls and clinical warnings.

OBJECTIVE: The aim of this study was to compare myocardial T2* assessment with region-based (RB) T2* multiecho technique (CMRtools) with the pixel-wise (PW) inline myocardial T2* mapping (Siemens) in patients with thalassemia major for myocardial iron characterization. MATERIALS AND METHODS: Forty-three thalassemia major patients were examined on a 1.5-T scanner using conventional gradient multiecho sequence. All the images were analyzed using both RB and PW T2* mapping. Coefficients of reproducibility (CRs) were used to assess the interoperator and intraobserver variability of each software. RESULTS: The mean (SD) myocardial T2* values using RB and PW software resulted significantly different (30.7 [15] milliseconds [range, 4.8-52.6 milliseconds] vs 24.3 [10.5] milliseconds [range 4.6-38.2 milliseconds]; P < 0.0001). Interestingly, we found that SD had exponential relationship with T2* with evidence of increase in SD for T2* values greater than 20 milliseconds. For myocardial T2* values less than 20 milliseconds, intraobserver CR was 1.2 milliseconds for RB and 1.8 milliseconds for PW T2* mapping, and the interoperator CR was 3.4 and 1.6 milliseconds for RB and PW T2* mapping, respectively. Comparing iron overload classification by both software, we found that 7 patients (16%) were differently categorized using the standard T2* thresholds. CONCLUSIONS: Our data show that RB and PW T2* mapping can be used interchangeably to measure severe myocardial and hepatic iron overload, whereas for borderline T2* values, we observed differences among the 2 methods causing different categorization.

Renal artery thrombosis. A case of acute flank pain in a patient with a new onset of renal failure and atrial fibrillation.

Renal artery thrombosis is a severe and often misdiagnosed entity, that represents a true medical emergency in which renal infarction can occur. The diagnosis is often a challenge for the emergency physicians since it can mimic other more common diseases, including renal colic. We report the case of an 82-year-old man who presented to our emergency department for abdominal pain, nausea, and vomiting resulting from right renal artery thrombosis and infarction caused by misdiagnosed atrial fibrillation. Starting from our experience, we recommend to always keep renal thromboembolism in the differential diagnosis in a patient with sudden onset of flank/abdominal pain, high levels of lactate dehydrogenase and/or haematuria since early diagnosis and proper treatment are the keys to rapid recovery.

Reversible supraventricular tachycardia and left bundle branch block in a marathon runner with exertional heat stroke in the Po Valley.

We report the case of a 52-year-old marathon runner admitted to our emergency department for exertional heat stroke (EHS). The electrocardiogram (ECG) showed a supraventricular tachycardia, probably an atrial flutter with 2:1 block, conducted with left bundle branch block. After 10 minutes of aggressive fluid management and rapid external cooling, the ECG returned to normal. As the high-sensitivity cardiac troponin I was elevated, coronary angiography and an electrophysiological study were performed, revealing normal coronary arteries and excluding inducible arrhythmias. As reported in the current literature, our findings confirm that the electrocardiographic changes and elevation of cardiac markers in EHS do not reflect cardiac ischemia, but rather a myocardial injury due to the pathophysiological response to dehydration and hyperthermia, which markedly impaired stroke volume and cardiac output. EHS is a life-threatening condition with a complex pathophysiology caused by thermoregulatory failure. Diagnosis is not always straightforward, but early recognition and timely management (the "golden hour") with rapid cooling and intravenous fluids are crucial to prevent irreversible and fatal organ damage. EHS is defined by a rectal temperature > 40.5 °C with symptoms or signs of neurological dysfunction, such as confusion, drowsiness, or seizures, which can rapidly worsen with delirium, coma, and cardiac arrest. With this case report, we want to remind emergency physicians that early diagnosis and appropriate management of EHS can avoid death and inappropriate treatment. (www.actabiomedica.it).

Hypovolemic shock due to Wunderlich syndrome (spontaneous renal haemorrhage): a case report and literature review.

Wunderlich syndrome (WS) or spontaneous renal haemorrhage is a rare and life-threatening condition often leading to haemorrhagic shock. WS is characterized by an acute onset of non-traumatic subcapsular and perirenal haematoma formation due to several causes, including neoplasms, cystic rupture, vasculitis, coagulopathies, and infections. The classical presentation includes acute flank or abdominal pain, a palpable flank mass and hypovolemic shock (Lenk's triad). Nausea, vomiting, fever, and haematuria can also be present. Computed tomography angiography is mandatory to localize the source of haemorrhage. Super-selective embolization can be performed to stop bleeding, while surgery is reserved to haemodynamic unstable patients and neoplastic cases. We describe a case of WS in a 79-year-old male patient, who rapidly developed hypovolemic shock requiring urgent nephrectomy.

Acute chest pain and dyspnoea as clinical presentation of primary membranous nephropathy. A case report and literature review.

Membranous nephropathy (MN) is the commonest cause of nephrotic syndrome (NS) in adult male patients worldwide. Most of the cases (80%) are idiopathic (primary MN, PMN), whereas about 20% are associated with autoimmune diseases, malignancies or exposures (secondary MN). PMN is a kidney-specific autoimmune glomerular disease mediated by antibodies to the M-type phospholipase A2 receptor (anti-PLA2R) (85%), thrombospondin type 1 domain containing 7A (THSD7A) (3-5%), or by other still unidentified mechanisms (10%). Most of the patients with PMN present with NS (80%). Clinical course of PMN is characterised by spontaneous remissions (40%) and relapses (15-30%). One third develop end-stage renal disease (ESRD) within 5 to 15 years from the onset. Anti-PLA2R/THSD7A antibodies levels correlate with proteinuria, clinical course, and outcomes. The treatment still remains matter of debate. Hypertension, proteinuria, and hyperlipidaemia must be treated in all patients. Immunosuppressive therapy is indicated in patients with elevated anti-PLA2R/THSD7A levels and proteinuria >3.5 g/d at diagnosis. With proper management, only 10% or less will develop ESRD over the subsequent 10 years. Here we report a case of a 34-year-old male patient with a ten-year history of asymptomatic PMN, treated with ACE-inhibitors, who presented to our emergency room for acute chest pain and exertional dyspnoea due to ESRD that required urgent dialysis. (www.actabiomedica.it).

A Case of Spontaneous Renal Haemorrhage (Wunderlich Syndrome) in an Anticoagulated Patient.

Spontaneous renal haemorrhage is a rare but severe condition known as Wunderlich syndrome (WS). The classic presentation includes sudden-onset flank pain, a palpable flank mass and hypovolaemic shock (Lenk's triad). WS can be due to neoplasms, vascular diseases, cystic rupture, coagulopathies and infections. A contrast-enhanced CT scan of the abdomen is mandatory for diagnosis. Surgery is reserved for haemodynamically unstable patients and those with neoplastic disease. We describe a case of WS in an anticoagulated patient with chronic atrial fibrillation, diabetes mellitus type 2 and hypertension, who developed acute renal failure and severe anaemia, that completely resolved with conservative treatment and discontinuation of anticoagulation therapy. LEARNING POINTS: Wunderlich syndrome refers to spontaneous renal or perinephric haemorrhage.Contrast-enhanced CT of the abdomen is the gold standard for diagnosis.Surgery should be reserved for haemodynamically unstable patients or those with neoplastic disease.

Kounis syndrome: from an unexpected case in the Emergency Room to a review of the literature.

Kounis syndrome (KS) is a coronary syndrome in the setting of allergic/anaphylactic reactions and can be classified in three variants: vasospastic allergic angina (type I), allergic myocardial infarction (type II) and stent thrombosis (type III). The early diagnosis is of paramount importance for the correct management and the prognosis, being KS a life-threatening emergency condition. KS is not uncommon, but it is frequently unrecognized or undiagnosed in virtue of its broad clinical manifestations. The diagnosis should be based on the combination of cardiovascular and allergic/anaphylactic clinical symptoms and signs, as well as on laboratory, electrocardiographic, echocardiographic, and angiographic evidence. ECG monitoring, cardiac enzymes and troponin are mandatory to confirm or exclude KS in a patient with subclinical or clinical, acute or chronic allergic reactions. Nevertheless, the treatment is a real challenge for the emergency clinicians because guidelines have not been established yet, and the therapy is based on the variant type. We herein report the case of type I KS in a woman with no prior history of allergy, admitted to our emergency department for abdominal pain, nausea and hematochezia. Starting from this case we conducted a systematic search of the following databases: PubMed, Google Scholar, Science Direct, Medline, using the keywords of "Kounis syndrome", "coronary spams", "cardiac arrest", "sudden death", "allergy", and "anaphylaxis". The main purpose of this review is to remind emergency clinicians to keep a high index of suspicion regarding KS when dealing with patients with allergic reactions or anaphylaxis to promptly identify and correctly manage KS.

From the Triage to the Intermediate Area: A Simple and Fast Model for COVID-19 in the Emergency Department.

INTRODUCTION: The early identification of patients with SARS-CoV-2 infection is still a real challenge for emergency departments (ED). First, we aimed to develop a score, based on the use of the lung ultrasonography (LUS), in addition to the pre-triage interview, to correctly address patients; second, we aimed to prove the usefulness of a three-path organization (COVID-19, not-COVID-19 and intermediate) compared to a two-path organization (COVID-19, non-COVID-19). METHODS: We retrospectively analysed 292 patients admitted to our ED from 10 April to 15 April 2020, with a definite diagnosis of positivity (93 COVID-19 patients) or negativity (179 not-COVID-19 patients) for SARS-COV-2 infection. Using a logistic regression, we found a set of predictors for infection selected from the pre-triage interview items and the LUS findings, which contribute with a different weight to the final score. Then, we compared the organization of two different pathways. RESULTS: The most informative factors for classifying the patient are known nasopharyngeal swab positivity, close contact with a COVID-19 patient, fever associated with respiratory symptoms, respiratory failure, anosmia or dysgeusia, and the ultrasound criteria of diffuse alveolar interstitial syndrome, absence of B-lines and presence of pleural effusion. Their sensitivity, specificity, accuracy, and AUC-ROC are, respectively, 0.83, 0.81, 0.82 and 0.81. The most significant difference between the two pathways is the percentage of not-COVID-19 patients assigned to the COVID-19 area, that is, 10.6% (19/179) in the three-path organization, and 18.9% (34/179) in the two-path organization (p = 0.037). CONCLUSIONS: Our study suggests the possibility to use a score based on the pre-triage interview and the LUS findings to correctly manage the patients admitted to the ED, and the importance of an intermediate area to limit the spread of SARS-CoV-2 in the ED and, as a consequence, in the hospital.

Inherited disorders of iron metabolism.

PURPOSE OF REVIEW: To discuss inherited iron disorders, their pathophysiology and clinical implications in the light of the recent advances in our knowledge of iron metabolism and its regulation. RECENT FINDINGS: In previous years the molecular mechanisms of cellular iron uptake and release and the cellular and systemic iron homeostasis have been substantially clarified. New proteins (hepcidin, hemojuvelin, HFE, TFR2 and ferroportin), mutated in hereditary hemochromatosis, have been identified with a crucial role in iron regulation. These advances have modified our understanding of the pathophysiology of hemochromatosis, now considered a disorder either due to hepcidin deficiency or (rarely) due to hepcidin resistance. Novel genetic forms of iron-related microcytic anemia have been identified, due to defects of iron transport/utilization or to TMPRSS6 deficiency and hepcidin hyperproduction, as occurs in iron-refractory iron deficiency anemia (IRIDA). A role for hepcidin has been identified also in acquired conditions, as in iron-loading anemias and in anemia of chronic diseases and inflammation. SUMMARY: Advances in basic research have improved the classification and diagnosis of genetic anemias and iron overload and are paving the way towards the development of drugs that target the molecular lesions.

Not all is COVID19: a case of eclampsia and posterior reversible encephalopathy syndrome in the emergency room.

In the so called COVID19 era, headache, fever and gastrointestinal symptoms are highly suggestive for SARS-CoV-2 infection, but in all the cases presenting to the emergency room, clinicians should always keep in mind alternative diagnoses, particularly if the patient is pregnant.  Life-threatening diseases, such as eclampsia and posterior reversible encephalopathy syndrome (PRES), should be promptly recognized and treated. Eclampsia is defined as a seizure occurring in association with pre-eclampsia, and it represents one of the major and serious obstetric disorders associated with significant maternal and perinatal morbidity and mortality. PRES is a distinctive clinical and imaging syndrome characterized by acute headaches, visual impairment, seizures, and altered sensorium, that can be associated with severe eclampsia. Emergency clinicians should always consider eclampsia in the differential diagnosis of headache in pregnant women. The prompt and accurate diagnosis of eclampsia/PRES is crucial to prevent adverse maternal and perinatal outcomes. Here we describe the case of a young pregnant woman admitted to our emergency department for fever, dyspnea, headache, nausea and vomiting, who developed generalized tonic clonic seizures and a subsequent status epilepticus due to eclampsia and PRES.

Skin Rash and Interstitial Pneumonia Can Be a Fatal Combination: A Rare Case of Anti-Melanoma Differentiation-Associated Gene 5 (MDA5)-Associated Interstitial Lung Disease.

We report the case of a 62-year-old male patient fully vaccinated for COVID-19, admitted to our emergency room for persistent fever associated with exertional dyspnoea, skin lesions, diffuse myalgias and arthralgias not responsive to broad-spectrum antibiotic and antiviral therapy, who developed a rapidly progressive refractory to treatment interstitial lung disease due to anti-melanoma differentiation-associated gene 5 (MDA5) antibodies, that required mechanical ventilation and ECMO. Here, we highlight the importance of always considering alternative diagnoses, i.e. viral and autoimmune diseases, including anti-MDA5 antibody screening, when dealing with patients with a skin rash, seronegative polyarthralgias and interstitial pneumonia, or acute respiratory distress syndrome of unknown origin. LEARNING POINTS: MDA5-associated dermatomyositis is a rare systemic syndrome associated with rapidly progressive and treatment-refractory interstitial lung disease.The anti-MDA5 antibody is the key biomarker for the diagnosis.Early diagnosis is crucial to promptly start aggressive immunosuppressive therapy with the aims of improving prognosis and reducing mortality.

A simple lung ultrasound protocol for the screening of COVID-19 pneumonia in the emergency department.

The most relevant manifestation of coronavirus disease 2019 (COVID-19) is interstitial pneumonia. Several lung ultrasound (US) protocols for pneumonia diagnosis are used in clinical practice, but none has been proposed for COVID-19 patients' screening in the emergency department. We adopted a simplified 6-scan lung US protocol for COVID-19 pneumonia diagnosis (LUSCOP) and compared its sensitivity with high resolution computed tomography (HRCT) in patients suspected for COVID-19, presenting to one Emergency Department from February 21st to March 15th, 2020, during the outbreak burst in northern Italy. Patients were retrospectively enrolled if both LUSCOP protocol and HRCT were performed in the Emergency Department. The sensitivity of LUSCOP protocol and HRCT were compared. COVID-19 pneumonia's final diagnosis was based on real-time reverse-transcription polymerase chain reaction from nasal-pharyngeal swab and on clinical data. Out of 150 suspected COVID-19 patients, 131 were included in the study, and 130 had a final diagnosis of COVID-19 pneumonia. The most frequent lung ultrasonographic features were: bilateral B-pattern in 101 patients (77%), B-pattern with subpleural consolidations in 26 (19.8%) and lung consolidations in 2 (1.5%). LUSCOP Protocol was consistent with HRCT in correctly screening 130 out of the 131 COVID-19 pneumonia cases (99.2%). In one case COVID-19 pneumonia was excluded by both HRCT and lung US. LUSCOP protocol showed optimal sensitivity and can be proposed as a simple screening tool for COVID-19 pneumonia diagnosis in the context of outbreak burst areas where prompt isolation of suspected patients is crucial for patients' and operators' safety.

Deep Vein Thrombosis and Pulmonary Embolism: Two Complications of COVID-19 Pneumonia?

Coronavirus disease 19 (COVID-19) is a worldwide infection which was recently declared a global health emergency by the WHO Emergency Committee. The most common symptoms are fever and cough, which can progress to pneumonia, acute respiratory distress syndrome (ARDS) and/or end-organ failure. Risk factors associated with ARDS and death are older age, comorbidities (e.g., hypertension, diabetes, hyperlipidaemia), neutrophilia, and organ and coagulation dysfunction. Disseminated intravascular coagulation and coagulopathy can contribute to death. Anticoagulant treatment is associated with decreased mortality in severe COVID-19 pneumonia. In this report we describe two patients with COVID-19 pneumonia who developed venous thromboembolism. LEARNING POINTS: Deep vein thrombosis and pulmonary embolism can occur in patients with COVID-19 pneumonia.Low-molecular-weight heparin prophylaxis does not decrease the risk of venous thromboembolism (VTE) in COVID-19 pneumonia.In the presence of clinical signs and/or suspicion of VTE, compression ultrasound and echocardiography should be always performed, irrespective of disease stage.

Diaphragmatic Rupture and Gastric Perforation in a Patient with COVID-19 Pneumonia.

We describe the case of a young female patient admitted to our emergency department during the Italian COVID-19 epidemic, for fever and dry cough associated with symptoms of gastric reflux over the previous 5 days. Lung ultrasound showed diffuse bilateral B lines with irregular pleural thickening, and consolidation with air bronchogram and slight pleural effusion in the lower left lobe. Chest HRCT and abdominal CT scanning with contrast revealed diaphragmatic rupture with gastric perforation, and atelectasis of the left pulmonary lobe with unilateral pleural effusion, diffuse ground-glass opacities and multiple small consolidations in both lobes. A nasopharyngeal swab for 2019-nCoV was positive. A diagnosis of diaphragmatic rupture and gastric perforation in COVID-19 pneumonia was made. The patient was immediately hospitalized and surgically treated. Treatment for COVID-19 and empiric antibiotic therapy were promptly started. LEARNING POINTS: Coronavirus disease (COVID-19) can cause fever, dry cough and acute respiratory failure.Cough can result in several complications, including rupture of the diaphragm and abdominal herniation.CT scanning is the gold standard technique to investigate COVID-19 pneumonia and diaphragmatic rupture.