NEPA (netupitant/palonosetron) for the antiemetic prophylaxis of nausea and vomiting induced by chemotherapy (CINV) with Folfirinox and Folfoxiri even during the COVID-19 pandemic: a real-life study.

OBJECTIVE: The outbreak of coronavirus disease 2019 (COVID-19) has affected the treatment of cancer patients, with particular regard to the management of both chemotherapy and side effects. Chemotherapy-induced nausea and vomiting (CINV) are amongst the most troublesome side effects that impair patients' adherence to treatments and their quality of life (QoL). NEPA (Akynzeo®), is an oral fixed-dose combination of netupitant [a neurokinin-1 receptor antagonist (NK1RA), 300 mg] and palonosetron [(5-hydroxytryptamine (serotonin or 5HT) type3 receptor antagonist (5HT3RA), 0.5 mg] which has been shown to be effective in preventing CINV. PATIENTS AND METHODS: This prospective study started before the outbreak of COVID-19 and was carried out during the pandemic period. The aim was to evaluate the efficacy and safety of a single oral dose NEPA plus 12 mg of dexamethasone (DEX) in patients treated with Folfoxiri plus Bevacizumab and Folfirinox. The patients were diagnosed with advanced colorectal cancer (CRC) or advanced pancreatic ductal adenocarcinoma (PDAC). They were divided into two groups: naïve patients and patients previously treated with serotonin receptor antagonists (5HT3-RA) and neurokin-1 receptor antagonists (NK1-RA). RESULTS: During the overall phase, the complete response (CR) rate was 96.8% in naïve patients treated with Folfoxiri plus Bevacizumab, and 94.6% in patients treated with Folfirinox. During the acute and delayed phases, the CR rate was 92.8% and 94.2%, with Folfoxiri and Bevacizumab, as well as 96.2% and 94.6%, with Folfirinox. There was no adequate control of CINV events in patients on antiemetic prophylaxis with 5HT3-RA or NK1-RA associated with cortisone. During the overall phase, the CR rate was 74.6% with Folfoxiri plus Bevacizumab and 75.8% with Folfirinox. During the acute and delayed phases, the CR rate was 72.5% and 74.8% with Folfoxiri plus Bevacizumab, as well as 75.2% and 74.6% with Folfirinox. CONCLUSIONS: This study has shown the therapeutic benefits of NEPA in the management and prophylaxis of CINV events, both in naive patients and patients previously treated with 5HT3-RA and NK1-RA. In addition, NEPA has been shown to be safe, both before and during the COVID-19 pandemic.

Impact of immunohistochemistry on the diagnosis and management of primary aldosteronism: An important tool for improved patient follow-up.

BACKGROUND AND AIMS: Primary aldosteronism is a common cause of secondary hypertension. Primary aldosteronism is caused by an aldosterone-producing adenoma or bilateral hyperplasia that in some cases is asymmetrical with one adrenal dominating aldosterone secretion. Most patients with aldosterone-producing adenoma are biochemically cured by unilateral adrenalectomy, but patients with bilateral hyperplasia have a significant risk of residual or recurrent disease. Here, immunohistochemistry of CYP11B1 and B2 was used to investigate whether these markers could aid in the diagnostic workup of primary aldosteronism patients. MATERIALS AND METHODS: A total of 39 patients with primary aldosteronism who underwent unilateral adrenalectomy for a presumed adenoma during 2013-2016 were included. Immunohistochemistry using monoclonal antibodies identifying the enzymes CYP11B1 and B2 was part of routine histopathological workup in 6 cases; in 33 cases, it was applied retrospectively. The hyperplasia diagnosis was suggested when there was no dominating nodule but immunoreactivity for CYP11B2 was seen in several nodules, which were also seen on routine sections. To distinguish between adenoma and hyperplasia, a ratio between the largest and second largest CYP11B2-positive nodules was calculated. RESULTS: In all, 22 patients had an aldosterone-producing adenoma, while 13 patients were judged to have hyperplasia. In four cases, a final diagnosis could not be established, thus these were judged equivocal. Among the 33 cases investigated retrospectively, the primary histopathological diagnosis was altered from hyperplasia to aldosterone-producing adenoma in 9 cases (27%) after immunohistochemistry, and the immunohistochemically rectified adenoma group displayed improved clinical cure rates compared to the routine H&E-diagnosed cohort. Moreover, the B2 ratio was significantly higher in adenoma than in hyperplasia and equivocal cases. CONCLUSION: Immunohistochemistry detecting CYP11B1 and B2 expression is of great help in establishing a final histopathological diagnosis in patients with primary aldosteronism. This procedure should be part of the histopathological routine in all operated primary aldosteronism patients.

[Forearm osteomusculocutaneous free filet flap for arm reconstruction after amputation as an alternative to shoulder disarticulation]. / Utilisation d'un lambeau libre ostéo-musculo-cutané total d'avant-bras.

We report the case of a 55-year-old woman suffering from a type I neurofibromatosis (also known as Von Recklinghausen neurofibromatosis) who was diagnosed with a high-grade schwannosarcoma of the median nerve, between the upper third and the medium third of the arm, upon contact with the humerus, invading the humeral vessels. The oncologic treatment of this tumour consisted in the amputation of the arm through the surgical neck of the humerus. In order to create a laterothoracic claw, to bring a partial function of the upper limb back, we decided to realize a free fillet forearm flap. This composite flap was composed of the radius and the ulna, all the forearm muscles and the skin of the anterior side of the forearm. A humeroradial plate osteosynthesis was done and the flap was then harvested with the radial pedicle, and anastomosed to the axillar artery. This procedure gave our patient a functional stump, giving back the arm functionality, especially the claw movement.

The production of reactive oxygen species in TLR-stimulated granulocytes is not enhanced by hyperglycemia in diabetes.

Toll-like receptors (TLRs) play an important role in several inflammatory diseases such as diabetes. The present study was to determine whether hyperglycemia in diabetes interferes in reactive oxygen species (ROS) production in granulocytes stimulated with either TLR2/zymosan, TLR4/lipopolysaccharide (LPS) or TLR2,4,9/concanavalin A (ConA). NADPH (nicotinamide adenine dinucleotide phosphate) oxidase and mitogen-activated protein kinase (MAPK) signaling pathways associated with ROS generation in TLR-stimulated granulocytes were evaluated. Our results demonstrate that ROS generation in resting granulocytes derived from patients suffering from Type 2 diabetes mellitus (T2DM) is significantly higher than that observed in equivalent cells from healthy controls. However, ROS formed by TLR-stimulated granulocytes from T2DM patients and healthy subjects were comparable. ROS production by TLR4,9 depends on NADPH-oxidase and MAPK signaling pathways. In contrast, the activation of TLR2 leads to ROS production by a mechanism that is dependent on NADPH oxidase but independent of the MAPK. In conclusion our results suggest that hyperglycemia in diabetes may prime cells metabolically for ROS generation but does not exert any significant effect on TLR-stimulated ROS production and possibly does not aggravate the development of ROS-dependent diabetic complications.

[Skin diversity: histological study of 140 skin residues, adapted to plastic surgery]. / La diversité de la peau : étude histologique de 140 résidus cutanés, adaptée à la chirurgie plastique.

UNLABELLED: We present in this original article a histological study of surgical skin residues. AIM OF THE STUDY: This study was realized in order to show, in objective way, skin diversity according to sex, age and area, and to illustrate some current surgical practices of our speciality. PATIENTS AND METHOD: Two years along, 141 patients was selected, 69 Men and 72 women. Fifty-four biopsies were realized on the upper extremity, 34 on the trunk and 53 on legs and arms. The histological study was based on two steps; the first one was a classic quantitative study, with measurement of each cutaneous layer, and objective evaluation of elastic density in superficial dermis. The second one was a descriptive histological analysis of each cutaneous area. RESULTS: The results coming from the quantitative analysis, allowed us to establish a classification of all the areas, according to each parameter. These results are globally compliant to the literature. The results of the descriptive analysis, lead us to conclude that it exists a lot of different skins with regional specificities. Then the crossover of the two analyses allowed us to define good practices tricks, in order to choose the best reconstruction technique for each area. CONCLUSION: This study is just a rough draft of a dynamic skin cartography adapted to our surgery. But it allowed us to confirm our basic premise: it doesn't exist only one skin but many skins.

[Temporary hearing threshold shift in policemen after firearm training]. / Spostamento temporaneo di soglia uditiva in agenti di polizia dopo esercitazioni in poligono di tiro.

BACKGROUND: The paper involves exposure to noise of the State Police officers connected with the use of firearms. The noise generated by these weapons is of short duration and high intensity. METHODS: The research was carried out during the sessions of firearm training of State Police officers to assess exposure to noise. RESULTS: The values of the various investigations, both audiometric and phonometric, carried out made it possible to demonstrate a significant exposure and a temporary increase in the threshold, above the frequency of 6000 Hz. CONCLUSION: Even taking account of the abatement from use of headphones, an exposure was demonstrated that was above the statutory limits, as was confirmed by the temporary hearing threshold shift.

TLR4 and RAGE: similar routes leading to inflammation in type 2 diabetic patients.

AIM: The present study investigates the interaction of TLR4 and RAGE with their respective ligands as inducers of the inflammatory markers IL-6 and TNF-α. Also, the reactivity of peripheral blood mononuclear cells (PBMNC) from type 2 diabetic (T2D) patients and non-diabetic healthy controls (ND) were comparatively studied. METHODS: Concentrations of IL-6 and TNF-α were measured by sandwich Elisa, using kits supplied by Assay Designs (Ann Arbor, MI, USA). PBMNC from T2D and ND were incubated in the presence or absence of LPS, anti-TLR4 or anti-RAGE for 72 hours at 37°C under 5% CO(2). The final volume was adjusted to 300 µL in DMEM supplemented with 10% fetal bovine serum. After incubation, the cells were centrifuged, the supernatant collected and the cytokines measured. RESULTS: PBMNC from T2D were more sensitive to innate immune stimulation with LPS and monoclonal agonist anti-TLR4 than were cells from ND. The actions of LPS, anti-TLR4 and anti-RAGE potentiated the production of IL-6 and TNF-α in both groups. The simultaneous activation of monoclonal anti-RAGE and anti-TLR4 suggests that both antibodies used different receptors on the cell surface, but converged on the same PBMNC signaling metabolic pathways. This simultaneous activation induced a higher production of IL-6 and TNF-α in PBMNC from the T2D patients than from the ND subjects. CONCLUSION: Our results clearly show an exacerbation of innate immunity in PBMNC with T2D that was possibly hyperglycaemia-induced. These data, when analyzed together, suggest the importance of innate immunity in the pathogenesis of T2D.

CT colonography before colonoscopy in subjects with positive faecal occult blood test. Preliminary experience.

PURPOSE: We report a preliminary evaluation of the performance of computed tomography colonography (CTC) systematically obtained before optical colonoscopy (OC) in subjects with positive faecal occult blood test (FOBT) within a population-based screening programme for colorectal cancer (CRC). MATERIALS AND METHODS: Seventy-nine subjects with positive FOBT from a regional screening programme were invited to perform same day CTC and OC. CTC was performed with standard bowel preparation. OC with segmental unblinding was the reference standard. A per-patient per-adenoma analysis was performed. RESULTS: Forty-nine of 79 subjects (62%) with positive FOBT adhered to the study and completed both examinations. Twenty-two (44.9%) of the 49 had a cancer or an adenoma ≥6 mm. Per-patient sensitivity, specificity, negative predictive value and positive predictive value for cancer or adenoma ≥6 mm were 95.5% (95%CI:77.2%-99.9%), 51.9% (95%CI:32.0%-71.3%), 93.3% (95%CI:68.1%-99.8%) and 61.8% (95%CI:43.6%-77.8%). CONCLUSIONS: In the setting of a FOBT-based screening programme for CRC, CTC showed a high sensitivity, but relatively low specificity and positive predictive value, for cancer and adenoma ≥6 mm. Probably performing CTC without faecal tagging as second line test after a positive FOBT is not a cost-effective strategy.

Increased ratio of mRNA expression of the genes CYP17 and CYP11B1 indicates autonomous cortisol production in adrenocortical tumors.

OBJECTIVE: Due to increased use of imaging techniques, adrenal incidentalomas are frequently detected. The majority are non-hyperfunctioning adrenocortical tumors. We have previously shown that expression of the gene CYP17, coding for the enzyme in the cortisol pathway, correlates with cortisol release from adrenocortical tumors in vitro. The aim of this study was to compare clinical data with mRNA expression of CYP17 and CYP11B1 in adrenocortical tumors from patients with and without Cushing's syndrome and to identify adrenal tumors that may cause subclinical Cushing's syndrome. DESIGN: A retrospective study of 34 patients undergoing adrenalectomy due to an adrenal tumor. METHODS: Clinical data were collected. In the adrenal gland the mRNA expression of the genes CYP17 and CYP11B1 was studied with in situ hybridisation technique. RESULTS: The median ratio of CYP17/CYP11B1 expression in tumors from patients with Cushing's syndrome was significantly higher than the median ratio in the non-hyperfunctioning tumors. Tumors from 2 patients with subclinical Cushing's syndrome had ratios within the upper range for non-hyperfunctioning tumors. CONCLUSIONS: The ratio between the expression of the genes CYP17 and CYP11B1 in tumors from patients with Cushing's syndrome is significantly higher than in the non-hyperfunctioning tumors. This indicates that 17alpha-hydroxylase is a major determinant of cortisol overproduction. The patients with subclinical Cushing's syndrome in this study are too few to draw any firm conclusions although the results suggest that subclinical Cushing's syndrome may be identified post-operatively with this method.

The role of adrenal scintigraphy in the preoperative management of primary aldosteronism.

BACKGROUND AND AIMS: Differentiation between the two major subgroups of primary aldosteronism, bilateral hyperplasia and aldosterone producing adenoma is essential since therapy in the former is medical and in the latter surgical. The aim of the present study was to evaluate the clinical utility of adrenocortical scintigraphy in the management of primary aldosteronism. MATERIAL AND METHODS: [131I] norcholesterol (NP-59) scintigraphy with dexamethasone suppression for subclassification and lateralization of primary aldosteronism was evaluated in 49 patients with long-term follow-up after diagnosis and treatment. RESULTS: Thirty-three patients with the diagnosis of aldosterone producing adenoma were operated with adrenalectomy. Preoperative scintigraphy showed lateralized isotope uptake in 27/33 patients while 6 showed no uptake. Twenty-two were cured and three significantly improved. Thus, in 25/33 (76%), scintigraphy showed the correct side as the patients benefited of surgery. Two patients did not improve. Fourteen patients with a probable diagnosis of bilateral hyperplasia had normal scintigraphies. CONCLUSIONS: In the present retrospective study we found limited sensitivity of NP-59 scintigraphy. However, when a lateralized scintigraphic uptake is achieved it has a high accuracy. Scintigraphy may be used as an adjunct in cases where adrenal venous sampling is inconclusive.

[Italian Program for Surveillance of Acute Pesticide-Related Illnesses: cases identified in 2005]. / Sistema di Sorveglianza delle Intossicazioni Acute da Fitosanitari: la casistica rilevata nel 2005.

In 2005, the Italian System for Surveillance of Acute Pesticide-Related Illnesses (SIAF) identified 625 cases, among which 520 unintentionally exposed. The majority of these subjects were men (75%) and aged 26-65 years (65%). About 63% of all exposures occurred at work. Severity for these illnesses was low for 94% and moderate for 5%. Four cases were classified as illnesses of high severity. Some 70% of all the reported exposures occurred between May and September. The active ingredients responsible for the largest number of cases were: glyphosate (n. 56), copper sulphate (n. 55), methomyl (n. = 52), metam-sodium (n. 24). Three episodes of collective environmental exposure to soil fumigants involving 23 subjects were also detected.

Analysis of burns caused by pre-filled gas canisters used for lamps or portable camping stoves.

The use of pre-filled valveless gas canisters for lamps or camping stoves has caused a number of serious burn incidents. We performed a retrospective analysis of all of the patients who were victims of such incidents admitted to the Marseille Burn Centre between January 1990 and March 2004. There were a total of 21 patients burned in such conditions. Adult males made up the majority of the victims of this sort. Lesions were often extensive (60% of the patients were burned over more than 10% of their body surface) and systematically deep. In order of frequency, burn locations were: the lower limbs, the upper limbs, the hands and the face. The incidents principally occurred during replacement of the canister near an open flame. The marketing of a canister with a valve in order to avoid gas leaks did not cause the old canisters to be taken off the market. On the contrary, European Safety Standard EN417, updated in October 2003, validated the use of these valveless canisters. The severity of the lesions caused and the existence of safe equivalent products requires the passage of a law that forbids valveless canisters.

[Symptoms and musculo-skeletal changes among personnel of the State Police exposed to mechanical risk]. / Sintomi ed alterazioni muscolo-scheletriche in personale della Polizia di Stato esposto a rischio biomeccanico.

The aim of this present study was to inquire about spine morfo-functional alterations among policemen with jobs regarded as potentially hazardous, in order to identify preclinical alterations of column and to plan adequate preventive measures. A physiopathologic and working anamnesis was carried out by means of questionnaire about personal data, jobs, reported rachidian symptomatology and presence of orthopedic diseases, given to policemen on duty in Bari. Every chosen worker was subject to orthopedic and neurological examination, radiography of column, Formetric tridimensional examination, telethermography of spine. We stratified the sample on the basis of age and job. Under the jobs we individuated 4 biomechanical hazardous activities, performed separately or together: driving motorcycle, driving car, flying helicopter, video terminal use. The whole sample, formed by 211 subjects, all male, had the average age of 39 years (Standard Deviation: +/- 4). About the reported rachidian symptomatology, only 41 (17, 98%) subjects were asymptomatical, contrary to clinical results, that were normal in almost the entire sample, with the exception of 3 workers (1, 31%), who had neurological clinical alterations. Structural alterations were checked by radiography among 64, 9% of subjects. The Formetric examination found alterations in different tract of rachis, also coexiting between each other. The telethermographic changes affected 63,99% of the sample and involved especially the lumbar tract (38,86%), dorsal region (18%) and cervical zone (7,1%). The relative frequency of dorsal tract increased with growing of age. The morfo-functional changes of the sample seem to depend rather on the performed job, than on degenerative process of age, partly because the average age of the sample is not much elevated and because the enlistment in Italian Police Force is subordinated to verification of optimum conditions, also characterized by absence of anomaly of column. The absence of clinical alteration, in contrast to reported rachidian symptomatology by 82,02% of subjects and with discovered objectivity, demands more clinical attention in presence of symptomatology and proposes supplementary non-invasive techiniques of investigation, as the telethermography and the formetric tridimensional examination.

Molecular connectivity methods for the characterization of surface energetics of liquids and polymers.

In the topological approach to structure-property relationships, the molecular structure is described in terms of appropriate weighted graphs to which suitable topological parameters, usually known as molecular connectivity indices, can be associated. Molecular connectivity indices are here applied to the prediction of surface free energy and Good-van Oss-Chaudhury acid-base components of organic compounds. To this aim, some quantitative structure-property relationships (QSPRs) are determined, involving both topological indices and group indicator variables of the customary functional group theory. The semiempirical models obtained to appear satisfactory and show significant advantages with respect to the models based on the purely functional group approach.

Hibernoma of the antero-lateral thigh.

Hibernoma is a rare benign tumour of brown fat. In most cases it presents as a voluminous slow-growing mass in the regions where remnants of brown fat can remain in adults. We report a case of a hibernoma on the thigh and present the diagnostic and therapeutic elements of this type of tumour, whose differential diagnosis of liposarcoma.

Anesthesiologic preoperative evaluation of drug addicted patient.

Even if there are few scientific data about preoperative management of drug addict patients, a careful anesthesiology evaluation facilitates the prevention of interactions between drugs and anaesthetics and avoids intraoperative and postoperative complications. Moreover it is important to earn the confidence of patient in order to know the abuse substances consumed and the frequency of consumption. This knowledge is necessary to the anaesthetist in order to manage possible withdrawal syndromes or overdose, which are the two greatest dangers for a drug addict patient during the hospital stay.

The solid surface free energy calculation; II. The limits of the Zisman and of the "equation-of-state" approaches.

This paper follows the "defense" of the Good-van Oss-Chaudhury (GvOC) acid-base approach made in Part I and carries out a detailed analysis of the Zisman critical surface energy and, mainly, of the Neumann equation-of-state (EQS) theory. The analysis is made on both a "practical" and a theoretical basis, trying to highlight the acceptable fitting results of axisymmetric drop shape analysis (ADSA) methods and their independence of the assumed thermodynamic foundations of EQS. Some new and original criticisms of the EQS approach are raised and it is shown that other purely semiempirical models, represented by different fitting equations with the same number of parameters, can represent the data measured by ADSA method with the same goodness as EQS. The equation of state appears as one of many semiempirical approaches for the evaluation of surface free energy of solids. Independent of the previous analysis, the criteria used in ADSA measurements are evaluated and some comments made on them.

The solid surface free energy calculation. I. In defense of the multicomponent approach.

The acid-base approach to the calculation of solid surface free energy and liquid-liquid interfacial tensions is a practical example of application of correlation analysis, and thus it is an approximate approach. In these limits, and provided that wide and well-obtained sets of contact angles or interfacial tension data are used for their computation, surface tension components can be considered as material properties. Although their numerical value depends on the characteristics of the chosen reference material, their chemical meaning is independent on the selected scale. Contact angles contain accessible information about intermolecular forces; using surface tension component (STC) acid-base theory, one can extract this information only making very careful use of the mathematical apparatus of correlation analysis. The specific mathematical methods used to obtain these results are illustrated by using as an example a base of data obtained by the supporters of the equation-of-state theory (EQS). The achievements are appreciably good and the agreement between STC and EQS is discussed.