Every year in Italy, influenza affects about 4 million people. Almost 5% of them are hospitalised. During peak illness, enormous pressure is placed on healthcare and economic systems. This study aims to quantify the clinical and economic burden of severe influenza during 5 epidemic seasons (2014-2019) from administrative claims data.

Patients hospitalized with a diagnosis of influenza between October 2014, and April 2019, were analyzed. Clinical characteristics and administrative information were retrieved from health-related Administrative Databases (ADs) of 4 Italian Local Health Units (LHUs). The date of first admission was set as the Index Date (ID). A follow-up period of six months after ID was considered to account for complications and re-hospitalizations, while a lookback period (2 years before ID) was set to assess the prevalence of underlying comorbidities.

Out of 2,333 patients with severe influenza, 44.1% were adults ≥ 65, and 25.6% young individuals aged 0-17. 46.8% had comorbidities (i.e., were at risk), mainly cardiovascular and metabolic diseases (45.3%), and chronic conditions (24.7%). The highest hospitalization rates were among the elderly (≥ 75) and the young individuals (0-17), and were 37.6 and 19.5/100,000 inhabitants/year, respectively. The average hospital stay was 8 days (IQR: 14 - 4). It was higher for older individuals (≥ 65 years, 11 days, [17 - 6]) and for those with comorbidities (9 days, [16 - 6]), p-value < 0.001. Similarly, mortality was higher in elderly and those at risk (p-value < 0.001). Respiratory complications occurred in 12.7% of patients, and cardiovascular disorders in 5.9%. Total influenza-related costs were €9.7 million with hospitalization accounting for 95% of them. 47.3% of hospitalization costs were associated with individuals ≥ 65 and 52.9% with patients at risk. The average hospitalisation cost per patient was € 4,007.

This retrospective study showed that during the 2014-2019 influenza seasons in Italy, individuals of extreme ages and those with pre-existing medical conditions, were more likely to be hospitalized with severe influenza. Together with complications and ageing, they worsen patient's outcome and may lead to a prolonged hospitalization, thus increasing healthcare utilization and costs. Our data generate real-world evidence on the burden of influenza, useful to inform public health decision-making.

Influenza virus affects the respiratory tract by direct viral infection or by damage from the immune system response. In humans, the respiratory epithelium is the only site where the hemagglutinin (HA) molecule is effectively cleaved, generating infectious virus particles. Virus transmission occurs through a susceptible individual's contact with aerosols or respiratory fomites from an infected individual. The inability of the lung to perform its primary function of gas exchange can result from multiple mechanisms, including obstruction of the airways, loss of alveolar structure, loss of lung epithelial integrity from direct epithelial cell killing, and degradation of the critical extracellular matrix.Approximately 30-40% of hospitalized patients with laboratory-confirmed influenza are diagnosed with acute pneumonia. These patients who develop pneumonia are more likely to be < 5 years old, > 65 years old, Caucasian, and nursing home residents; have chronic lung or heart disease and history of smoking, and are immunocompromised.Influenza can primarily cause severe pneumonia, but it can also present in conjunction with or be followed by a secondary bacterial infection, most commonly by Staphylococcus aureus and Streptococcus pneumoniae. Influenza is associated with a high predisposition to bacterial sepsis and ARDS. Viral infections presenting concurrently with bacterial pneumonia are now known to occur with a frequency of 30-50% in both adult and pediatric populations. The H3N2 subtype has been associated with unprecedented high levels of intensive care unit (ICU) admission.Influenza A is the predominant viral etiology of acute respiratory distress syndrome (ARDS) in adults. Risk factors independently associated with ARDS are age between 36 and 55 years old, pregnancy, and obesity, while protective factors are female sex, influenza vaccination, and infections with Influenza A (H3N2) or Influenza B viruses.In the ICU, particularly during the winter season, influenza should be suspected not only in patients with typical symptoms and epidemiology, but also in patients with severe pneumonia, ARDS, sepsis with or without bacterial co-infection, as well as in patients with encephalitis, myocarditis, and rhabdomyolysis.

To investigate different etiologies and management of the rhabdomyolysis in children.

Eight pediatric rhabdomyolysis cases who applied to the Dokuz Eylul University Faculty of Medicine Department of Pediatric Nephrology with different etiologies between January 2004 and January 2012 were evaluated in terms of age, gender, admission symptoms, physical examination findings, factors provoking rhabdomyolysis, number of rhabdomyolysis attacks, laboratory results, family history and the final diagnosis received after the treatment.

Average diagnosis ages of eight cases were 129 (24-192) ± 75.5 mo and five of them were girls. All of them had applied with the complaint of muscle pain, calf pain, and dark color urination. Infection (pneumonia) and excessive physical activity were the most important provocative factors and excessive licorice consumption was observed in one case. In 5 cases, acute kidney injury was determined and two cases needed hemodialysis. As a result of the further examinations; the cases had received diagnoses of rhabdomyolysis associated with mycoplasma pneumoniae, sepsis associated rhabdomyolysis, licorice-induced hypokalemic rhabdomyolysis, carnitine palmitoyltransferase II deficiency, very long-chain acyl-CoA dehydrogenase deficiency, congenital muscular dystrophy and idiopathic paroxysmal rhabdomyolysis (Meyer-Betz syndrome).

It is important to distinguish the sporadic and recurrent rhabdomyolysis cases from each other. Recurrent rhabdomyolysis cases should follow up more regardful and attentive.

Polymyalgia rheumatica (PMR) is relatively common among the elderly, and is characterized by multiple body aches with an elevated erythrocyte sedimentation rate. Even though the etiology of PMR remains unknown, a number of infectious agents have been suggested to cause PMR. Also, there are reports of PMR after influenza vaccination. The exact role of influenza vaccination on the development of PMR remains unknown, but may be associated with specific human leukocyte antigens (HLAs), such as HLA-DRB1 and HLA-DQB1. Whether postvaccination PMR is caused by influenza virus antigen or adjuvants in the vaccine is another unanswered question. We herein report a case of an 85-year-old woman who developed PMR shortly after contracting influenza virus B. Even though infections are hypothesized to be one of the causes of PMR, this is the first-ever case of PMR following influenza virus infection. Further studies may elucidate the exact role of influenza virus infection on the etiology and pathogenesis of PMR.

Renal complications of influenza A virus infections are uncommon but can contribute to a deterioration in the patient's condition, which include acute kidney injury (AKI) in critically ill patients, rhabdomyolysis, hemolytic uremic syndrome (HUS), acute glomerulonephritis (AGN), disseminated intravascular coagulation (DIC), Goodpasture's syndrome, and acute tubulointerstitial nephritis (TIN). The clinical characteristics of AKI in critically ill patients with pandemic influenza A(H1N1) 2009 virus (A(H1N1)pdm09) infection are similar to uninfected patients. Underlying conditions associated with AKI include older age, diabetes mellitus, obesity, pregnancy, history of asthma, and chronic kidney disease. Histologic examination of the kidneys from patients with A(H1N1)pdm09 infection who died include acute tubular necrosis (ATN), myoglobin pigment, and DIC. A(H1N1)pdm09 is present in the kidneys of some patients. The clinical characteristics of patients with rhabdomyolysis associated with influenza A include younger age and the frequent occurrence of muscle symptoms. AKI occurs in approximately one third of patients with rhabdomyolysis due to influenza A. HUS is associated with A(H1N1)pdm09 as follows: Streptococcus pneumoniae-associated HUS following A(H1N1)pdm09 infection, HUS triggered by A(H1N1)pdm09 in patients with genetic complement dysregulation, and HUS associated with A(H1N1)pdm09 without known underlying disorder. AGN, Goodpasture's syndrome, and acute TIN are extremely rare complications of influenza A virus infection. Although the pathogenesis underlying renal injuries due to influenza A virus has not been delineated, some hypotheses have been advanced, including ATN due to renal hypoperfusion or rhabdomyolysis, glomerular microthrombosis due to DIC, direct viral injury to the kidney, and an altered immune system with systemic mononuclear cell activation following influenza A virus infections.

Influenza B-associated rhabdomyolysis (IBAR) is an infrequent and little-known complication of influenza B virus infection in children. Diagnosis is usually made based on clinical history, the presence of influenza in the community and detection of virus in nasopharyngeal specimens. The aim of this study was to describe the clinical and laboratory manifestations, complications and outcomes of IBAR in Taiwanese children.

A retrospective analysis was conducted in patients aged < 17 years who had been diagnosed with IBAR at a university children's hospital in North Taiwan during 2000-2007. All children enrolled in the study had presented with rhabdomyolysis associated with laboratory-confirmed influenza B infections. Demographic data, clinical manifestations, complications and outcomes were included in the analysis.

Overall, 24 IBAR cases were analysed. IBAR typically occurred in school-aged children with a 7:3 male:female ratio. The mean age was 7.2 ± 1.9 years. Nearly 63% of cases occurred between the ages of 6 and 9 years. The median interval between the onset of influenza and onset of IBAR was 3.4 days (range, 1-14). The calf muscles were involved in all cases. Laboratory tests indicated a mean initial blood creatine kinase of 4212 U/L. The median time to clinical recovery was 5 days (range 1-24). No patient had renal failure. IBAR tends to occur mainly in winter and spring during influenza B outbreaks. IBAR sometimes induces some complications, and early detection and careful medical treatment are necessary.

The results of this study indicate that outcomes of IBAR are good with proper medical care.

Rhabdomyolysis is a common clinical syndrome and accounts for 7% of all cases of acute kidney injury (AKI) in the USA. It can result from a wide variety of disorders, such as trauma, exercise, medications and infection, but in the pediatric population, infection and inherited disorders are the most common causes of rhabdomyolysis. Approximately half of patients with rhabdomyolysis present with the triad of myalgias, weakness and dark urine. The clinical suspicion, especially in the setting of trauma or drugs, is supported by elevated creatinine kinase levels and confirmed by the measurement of myoglobin levels in serum or urine. Muscle biopsy and genetic testing should be performed if rhabdomyolysis is recurrent or metabolic myopathy is suspected. Early recognition is important to prevent AKI through the use of aggressive hydration. Prevention is important in patients with inherited forms, but novel therapies may be developed with the better understanding of the pathophysiology and genetics of rhabdomyolysis.

Influenza is an acute febrile illness caused by influenza A or B viruses. It occurs mainly in winter in temperate climates, and throughout the year in tropical Australia. It is highly contagious and of considerable public health concern because of the rapidity with which epidemics evolve and the associated morbidity and mortality. Most influenza illnesses resolve over about 1 week without specific medical intervention. People at particular risk for complicated infection are those > 65 or < 5 years old, those with chronic medical comorbidities, residents of chronic care facilities (including nursing homes), and women in the second or third trimester of pregnancy. Complicated influenza infection most commonly manifests as primary viral pneumonia, combined viral and bacterial pneumonia, and secondary bacterial pneumonia. Rare but serious complications of influenza include central nervous system involvement (eg, encephalitis, transverse myelitis, aseptic meningitis, and Guillain-Barré syndrome). The recent emergence of avian influenza A/H5N1 and confirmation of sporadic cases of human H5N1 infection have heightened concern about an impending human influenza pandemic, either from a human form of H5N1 or a primary new human influenza strain. H5N1 infection in humans has been associated with severe illness and a > 50% mortality rate, with high mortality in people aged 10-39 years.

Renal involvement in influenza A virus infection has been rarely reported. To define the clinical characteristics and the factors contributing to the development of renal involvement in influenza A virus infection, we reviewed the clinical characteristics, laboratory data, pediatric risk of mortality (PRISM) score, and the number of systemic inflammatory response syndrome (SIRS) criteria and dysfunctional organs in 45 hospitalized children with influenza A virus infection. Eleven (24.4%) patients had renal involvement. All patients with renal involvement suffered from sepsis and multiple organ dysfunction syndrome (MODS) and 5 developed acute renal failure (ARF). The incidences of dehydration, hypotension, disseminated intravascular coagulation (DIC), and rhabdomyolysis were significantly higher in patients with renal involvement. PRISM scores, the numbers of SIRS criteria and dysfunctional organs, and mortality rate were also higher in patients with renal involvement. Influenza A RNA was absent in the renal tissues of 3 patients with ARF. These results suggested that renal involvement in influenza A virus infection occurred in patients with sepsis and MODS; dehydration, hypotension, DIC, and rhabdomyolysis were factors contributing to its development; direct viral injury to the kidney did not seem to occur in influenza A virus infection.

Although rhabdomyolysis is an uncommon disorder, especially in children, it can present as a severe, life-threatening event. Paediatricians need to be aware of this important, probably underdiagnosed disorder in order to implement appropriate early treatment. In this report, seven children with rhabdomyolysis of both forms, endogenous and exogenous, are presented. Despite comprehensive 'up-to-date' investigations being performed on paediatric patients with endogenous (often recurrent) rhabdomyolysis, the majority of these patients' underlying disorders will remain undiagnosed. Overall, these patients usually have a very good prognosis even if repeated, severe life-threatening episodes occur. It is recommended that a regimen of early therapy with fluids and sodium bicarbonate be instituted in all patients with rhabdomyolysis.

Rhabdomyolysis is a relatively common condition that may occur intermittently in chronic and inflammatory myopathy, muscular dystrophy, and metabolic myopathy. Rhabdomyolysis can also present acutely in otherwise healthy individuals. The list of etiologies for acute muscle cell lysis is enormous, with new causes described yearly. Series on acute pediatric rhabdomyolysis have not yet been published. This article describes a retrospective review of children admitted to the authors' institution during an 8-year period in whom rhabdomyolysis was recognized as a complication during their hospital stay. Patients with intermittent or relapsing rhabdomyolysis were excluded. Nineteen children were identified. Trauma (five cases), nonketotic hyperosmolar coma (two cases), viral myositis (two cases), dystonia (two cases), and malignant hyperthermia-related conditions (two cases) were the most common causes of rhabdomyolysis. Acute renal failure was the most frequent complication, occurring in 42% of cases. The mean age of renal failure patients was 13.9 years, compared to 8 years for non-renal failure children. Careful assessment of the initial urinalysis would have suggested a diagnosis of rhabdomyolysis in 9 of 16 patients tested.