A Case Report of New-Onset Diabetes Mellitus as an Early Warning Sign of Pancreatic Ductal Adenocarcinoma in an Elderly Patient: The Earlier the Diagnosis and Surgery, the Better the Prognosis.

Studies have been recently conducted to find pancreatic ductal adenocarcinoma (PDAC) in high-risk groups by identifying individuals with pancreatic cystic lesions and elderly people (> 50 years) with new-onset diabetes mellitus (NODM). We report the case of a 91-year-old woman in good health with pancreatic cysts, who firstly displayed a NODM and, one month later, a PDAC. A dehydration syndrome with polydipsia and asthenia led to her hospitalization. High levels of blood glucose and glycated hemoglobin were found. An abdomen US showed a minute pancreas with some cysts. Rehydration and insulin therapy led to a good glycemic compensation. One month after discharge, she displayed weight loss, diarrhea, and jaundice. On the second admission, high levels of total and direct bilirubin, indices of hepatic cholestasis, and Ca 19.9 were found. An abdomen contrast medium CT evidenced a nodule at the pancreatic head, suggesting a malignant lesion, and dilatation of both the Wirsung duct and the whole biliary tract. Despite the lack of a histological diagnosis, the absence of signs of local invasion, metastasis, and co-morbidities as well as the rapid clinical deterioration led us to propose surgical treatment. A few days later, a pancreatoduodenectomy was performed. The histologic examination showed a moderately differentiated (G2) PDAC. The TNM staging was IIA (pT3, N0, M0) (R0). Three weeks after, she was discharged with normal liver function tests, Ca 19.9 levels, and a good glycemic compensation with insulin therapy. Five years after surgical treatment, she is still doing well displaying a normal abdomen CT follow-up, normal blood tests, including Ca 19.9, and a good glycemic compensation. Our case report denotes an exceptional duration of survival of PDAC and highlights the importance to seek its presence in every case of NODM in patients > 50 years, especially if they carry pancreatic cysts.

Predictors of poor outcome in tocilizumab treated patients with Sars-CoV-2 related severe respiratory failure: A multicentre real world study.

INTRODUCTION: Despite Tocilizumab is now recognized as a concrete therapeutic option in patients with severe SARS-CoV-2 related respiratory failure, literature lacks about factors influencing the response to it in this context. Therefore, the aim of our study was to provide evidence about predictors of poor outcome in Tocilizumab treated patients in the real-world practice. MATERIALS AND METHODS: We retrospectively analyzed clinical, laboratory and chest computer tomography (CCT) data of patients firstly admitted in non Intensive Care Units (ICU) and suffering from severe respiratory failure, who were treated with the IL-6 antagonist Tocilizumab. We compared patients who died and/or required admission to ICU with oro-tracheal intubation (OTI) with those who did not. RESULTS: Two hundreds and eighty-seven patients (29.9% females) with mean age ± SD 64.1 ± 12.6 years were the study population. In-hospital mortality was 18.8%, while the composite endpoint in-hospital mortality and/or ICU admission with OTI occurred in 23.7%. At univariate analysis, patients who died and/or were admitted to ICU with OTI were significantly older and co-morbid, had significantly higher values of creatinine, C-reactive protein (CRP) and procalcitonin and lower lymphocytes count, PaO2/FiO2 ratio (P/F) and room air pulsossimetry oxygen saturation (RAO2S) at hospital admission. Computed tomography ground glass opacities (CT-GGO) involving the pulmonary surface ≥ 50% were found in 55.4% of patients who died and/or were admitted to ICU with OTI and in 21.5% of patients who did not (p=0.0001). At multivariate analysis, age ≥ 65 years (OR 17.3, 95% CI: 3.7-81.0), procalcitonin ≥ 0.14 (OR 9.9, 95%CI: 1.7-56.1), RAO2S ≤ 90% (OR 4.6, 95%CI: 1.2-17.0) and CCT-GGO involvement ≥ 50% (OR 5.1, 95%CI: 1.2-21.0) were independent risk factors associated with death and/or ICU admission with OTI. CONCLUSION: Tocilizumab has shown to improve outcome in patients with severe respiratory failure associated to SARS-CoV-2 related pneumonia. In our multicentre study focusing on Tocilizumab treated severe COVID-19 patients, age ≥ 65 years, procalcitonin ≥ 0.14 ng/mL, RAO2S ≤ 90% and CCT-GGO involvement ≥ 50% were independent factors associated with poor outcome.

The incremental value of computed tomography of COVID-19 pneumonia in predicting ICU admission.

Triage is crucial for patient's management and estimation of the required intensive care unit (ICU) beds is fundamental for health systems during the COVID-19 pandemic. We assessed whether chest computed tomography (CT) of COVID-19 pneumonia has an incremental role in predicting patient's admission to ICU. We performed volumetric and texture analysis of the areas of the affected lung in CT of 115 outpatients with COVID-19 infection presenting to the emergency room with dyspnea and unresponsive hypoxyemia. Admission blood laboratory including lymphocyte count, serum lactate dehydrogenase, D-dimer and C-reactive protein and the ratio between the arterial partial pressure of oxygen and inspired oxygen were collected. By calculating the areas under the receiver-operating characteristic curves (AUC), we compared the performance of blood laboratory-arterial gas analyses features alone and combined with the CT features in two hybrid models (Hybrid radiological and Hybrid radiomics)for predicting ICU admission. Following a machine learning approach, 63 patients were allocated to the training and 52 to the validation set. Twenty-nine (25%) of patients were admitted to ICU. The Hybrid radiological model comprising the lung %consolidation performed significantly (p = 0.04) better in predicting ICU admission in the validation (AUC = 0.82; 95% confidence interval 0.73-0.97) set than the blood laboratory-arterial gas analyses features alone (AUC = 0.71; 95% confidence interval 0.56-0.86). A risk calculator for ICU admission was derived and is available at: https://github.com/cgplab/covidapp . The volume of the consolidated lung in CT of patients with COVID-19 pneumonia has a mild but significant incremental value in predicting ICU admission.

Dyspnea and leg effort during exercise.

Dyspnea and leg effort are the major symptoms limiting exercise in healthy subjects and in patients with a variety of respiratory disorders. Quantitative measurement of both symptoms may be obtained by category scales such as VAS and Borg, with the latter being widely used. Furthermore, descriptor clusters of dyspnea help to assess some of the reasons for stopping exercise. The intensity of dyspnea and leg effort are similar in different disease states; this symmetry suggests that the limiting discomfort is a function of the intensity of increased motor drive to peripheral and respiratory muscles. An alternative explanation for the factors which limit exercise is that the subjects stop exercise volitionally when the discomfort associated with continuing exercise exceeds that which they are willing to tolerate. Muscle strength contributes to the intensity of dyspnea and leg effort at a given power output: the greater the muscle force, the lower the symptom. Symptoms also correlate with intensity and duration of a task by a power function in such a way that when minimizing the intensity of a given muscular task by prolonging the duration of activity, the symptom is drastically reduced. Skeletal muscle fatigue may be a factor limiting exercise tolerance both in healthy subjects and in patients with cardiorespiratory disorders. In conclusion, symptom measurement complements physiological measurements, both being essential to a comprehensive understanding of exercise tolerance.

Respiratory muscles and dyspnea in obese nonsmoking subjects.

To our knowledge no data have been reported on the contribution to acute increase in dyspnea by the respiratory muscles in obese nonsmoking subjects. To better focus on this topic, we studied seven obese subjects and an age-matched normal control group, assessing baseline pulmonary function, breathing pattern, esophageal pressure (Pes), and gastric (Pga) and transdiaphragmatic (Pdi) pressures. Pes was also recorded during a sniff maneuver (Pessn). During a hypercapnic rebreathing test we recorded inspiratory swing in Pes (Pessw), expiratory changes in Pga, and inspiratory swings in Pdi (Pdisw). Change in inspiratory capacity was considered the mirror image of end-expiratory lung volume (EELV). Dyspnea was assessed by a modified Borg scale. Under control conditions, patients exhibited a reduced expiratory reserve volume and intrinsic positive end-expiratory pressure (PEEPi). At the end of hypercapnic stimulation, compared with controls our obese subjects exhibited greater respiratory frequency (Rf), shorter expiratory time, greater Pessw, and lower Pdisw. Increases in EELV and PEEPi were found in the obese subjects but not in controls. Changes in Borg correlated with changes in PETCO2, VE, Pessw (%Pessn), and Pdisw to a greater extent in patients than in controls. Stepwise regression analysis indicated the amount of variability in Borg that was predicted by both Pdisw (r2 = 0.31, p < 0.0004), and Pessw (%Pessn) (r2 = 0.09, p < 0.005) in controls, and by Pessw (%Pessn) (r2 = 0.40, p < 0.00001) in obese subjects. We conclude that the rib cage muscles contributed to dyspnea to a greater extent in this subset of obese subjects.

Effects of rapid saline infusion on lung mechanics and airway responsiveness in humans.

Lung mechanics and airway responsiveness to methacholine (MCh) were studied in seven volunteers before and after a 20-min intravenous infusion of saline. Data were compared with those of a time point-matched control study. The following parameters were measured: 1-s forced expiratory volume, forced vital capacity, flows at 40% of control forced vital capacity on maximal (Vm(40)) and partial (Vp(40)) forced expiratory maneuvers, lung volumes, lung elastic recoil, lung resistance (Rl), dynamic elastance (Edyn), and within-breath resistance of respiratory system (Rrs). Rl and Edyn were measured during tidal breathing before and for 2 min after a deep inhalation and also at different lung volumes above and below functional residual capacity. Rrs was measured at functional residual capacity and at total lung capacity. Before MCh, saline infusion caused significant decrements of forced expiratory volume in 1 s, Vm(40), and Vp(40), but insignificantly affected lung volumes, elastic recoil, Rl, Edyn, and Rrs at any lung volume. Furthermore, saline infusion was associated with an increased response to MCh, which was not associated with significant changes in the ratio of Vm(40) to Vp(40). In conclusion, mild airflow obstruction and enhanced airway responsiveness were observed after saline, but this was not apparently due to altered elastic properties of the lung or inability of the airways to dilate with deep inhalation. It is speculated that it was likely the result of airway wall edema encroaching on the bronchial lumen.