Prevention and the treatment of oral mucositis: the efficacy of sodium bicarbonate vs other agents: a systematic review.

INTRODUCTION: Oral mucositis (OM) is a major side effect of cancer therapy, which is associated with significant symptoms, treatment delays and increased costs for the health system. It is an important component of the quality of life of cancer patients and, until now, there has been no gold standard regarding prevention or treatment of this pathology. Notwithstanding the paucity of treatment guidelines (due to limited evidence from high-quality, rigorous studies), sodium bicarbonate (SB) rinses are one of the most used agents for OM management. OBJECTIVES: A systematic review (2000-2022) was performed in order to compare and examine different agents versus sodium bicarbonate (SB) in preventing or treating OM. SOURCES: Eleven randomized controlled trials (RCT) were evaluated: four were conducted for the prevention and seven for the management of OM. The risk of bias of RCTs was assessed using the revised Cochrane risk of bias tool for randomized trials. STUDY SELECTION: According to the RoB2 evaluation for randomized trials, four RCTs were judged to be at a high risk of bias, two were rated as 'problematic', while five were deemed to be a low risk of bias. CONCLUSIONS: The results revealed that there was no evidence for supporting SB in OM treatment regarding management and prevention. CLINICAL SIGNIFICANCE: Results showed in this review takes on a strategic importance in the use of SB for OM management or prevention; indiscriminate use of SB could be counterproductive because it causes a sudden pH increase and it delays proper OM pharmacological treatment.

17-AAG and Apoptosis, Autophagy, and Mitophagy in Canine Osteosarcoma Cell Lines.

Canine osteosarcoma is highly resistant to current chemotherapy; thus, clarifying the mechanisms of tumor cell resistance to treatments is an urgent need. We tested the geldanamycin derivative 17-AAG (17-allylamino-17-demethoxygeldanamycin) prototype of Hsp90 (heat shock protein 90) inhibitors in 2 canine osteosarcoma cell lines, D22 and D17, derived from primary and metastatic tumors, respectively. With the aim to understand the interplay between cell death, autophagy, and mitophagy, in light of the dual effect of autophagy in regulating cancer cell viability and death, D22 and D17 cells were treated with different concentrations of 17-AAG (0.5 µM, 1 µM) for 24 and 48 hours. 17-AAG-induced apoptosis, necrosis, autophagy, and mitophagy were assessed by transmission electron microscopy, flow cytometry, and immunofluorescence. A simultaneous increase in apoptosis, autophagy, and mitophagy was observed only in the D22 cell line, while D17 cells showed low levels of apoptotic cell death. These results reveal differential cell response to drug-induced stress depending on tumor cell type. Therefore, pharmacological treatments based on proapoptotic chemotherapy in association with autophagy regulators would benefit from a predictive in vitro screening of the target cell type.

Intention to leave, depersonalisation and job satisfaction in physicians and nurses: a cross-sectional study in Europe.

The European healthcare sector faces a significant shortage of healthcare workers. Assessing the prevalence of this issue and understanding its direct and indirect determinants are essential for formulating effective recruitment programs and enhancing job retention strategies for physicians and nurses. A multicentric cross-sectional study was conducted, involving 381 physicians and 1351 nurses recruited from eight European hospitals in Belgium, the Netherlands, Italy, and Poland. The study focused on assessing turnover intentions among healthcare workers based on the Job Demands-Resources model, using an online questionnaire. Structural equation models were employed to test the data collection questionnaires' construct validity and internal consistency. The turnover intention was assessed by agreement with the intention to leave either the hospital or the profession. Among physicians, 17% expressed an intention to leave the hospital, while 9% intended to leave the profession. For nurses, the figures were 8.9% and 13.6%, respectively. The internal consistency of the questionnaires exceeded 0.90 for both categories of health workers. Depersonalization and job dissatisfaction were identified as direct determinants of turnover intention, with work engagement being particularly relevant for nurses. We found a higher intention to leave the hospital among physicians, while nurses were more prone to leave their profession. To mitigate turnover intentions, it is recommended to focus on improving job satisfaction, work engagement and fostering a positive working climate, thereby addressing depersonalisation and promoting job retention.

Feline ovarian tissue vitrification: The effect of fragment size and base medium on follicular viability and morphology.

To achieve optimal vitrification, tissue structure and fragment size represent a challenge for obtaining sufficient cooling velocity. Theoretically, thin ovarian tissue fragments lead to higher surface contact, hence higher solute penetration. Another critical factor is the concentration of cryoprotectants (CPA): CPA toxicity may occur with high concentrations, and as such, this may induce local apoptosis. Therefore two experiments were conducted: In experiment I, we compared the effect of sucrose supplementation in vitrification solution along with ovarian fragments of different sizes on post-warming tissue viability and follicle architecture. Fragments of two different sizes, with a thickness and radius of 1.5 × 0.75 mm and 3 × 1.5 mm respectively were vitrified in vitrification solution without sucrose and with 0.5 M sucrose supplementation. Post-warming, fragments of ovarian tissue (fresh and vitrified) were evaluated for viability (Calcein AM/Propidium Iodide) and for morphology (hematoxylin-eosin). In experiment II, we aimed to reduce cryoprotectant toxicity by using lower CPA concentrations in combination with an optimized carrier medium (HypThermosol®; HTS). Ovarian tissue fragments were randomly allocated to five groups (A: fresh controls; B: vitrified in GLOBAL® TOTAL® LP w/HEPES with 15% ethylene glycol (EG) and 15% DMSO; C: vitrified in HTS with 5% EG and 5% DMSO; D: vitrified in HTS with 10% EG and 10% DMSO; E: vitrified in HTS with 15% EG and 15% DMSO). Fragments (fresh and vitrified) were evaluated for morphology (hematoxylin-eosin) and for apoptosis through the activity of caspase-3. Results showed that follicular morphology was affected by the size of the fragment; smaller sized fragments contained a greater proportion of intact follicles (53.8 ± 2.0%) compared to the larger fragments (40.3 ± 2.0%). Our results demonstrated that 1.5 × 0.75 mm sized pieces vitrified in a vitrification solution supplemented with 0.5 M sucrose had more intact follicles (54.8 ± 1.3%; P = 0.0002) after vitrification. In addition, HTS presented no additional protective effect as a base medium, neither for follicular morphology nor apoptotic rate.

Clinical significance and in vitro cellular regulation of hypoxia mimicry on HIF-1α and downstream genes in canine appendicular osteosarcoma.

Cellular adaptation to a hypoxic microenvironment is essential for tumour progression and is largely mediated by HIF-1α and hypoxia-regulated factors, including CXCR4, VEGF-A and GLUT-1. In human osteosarcoma, hypoxia is associated with resistance to chemotherapy as well as with metastasis and poor survival, whereas little is known about its role in canine osteosarcoma (cOSA). This study aimed primarily to evaluate the prognostic value of several known hypoxic markers in cOSA. Immunohistochemical analysis for HIF-1α, CXCR4, VEGF-A and GLUT-1 was performed on 56 appendicular OSA samples; correlations with clinicopathological features and outcome was investigated. The second aim was to investigate the in vitro regulation of markers under chemically induced hypoxia (CoCl2). Two primary canine osteosarcoma cell lines were selected, and Western blotting, immunofluorescence and qRT-PCR were used to study protein and gene expression. Dogs with high-grade OSA (35.7%) were more susceptible to the development of metastases (P = 0.047) and showed high HIF-1α protein expression (P = 0.007). Moreover, HIF-1α overexpression (56%) was correlated with a shorter disease-free interval (DFI; P = 0.01), indicating that it is a reliable negative prognostic marker. The in vitro experiments identified an accumulation of HIF-1α in cOSA cells after chemically induced hypoxia, leading to a significant increase in GLUT-1 transcript (P = 0.02). HIF-1α might be a promising prognostic marker, highlighting opportunities for the use of therapeutic strategies targeting the hypoxic microenvironment in cOSA. These results reinforce the role of the dog as a comparative animal model since similar hypoxic mechanisms are reported in human osteosarcoma.

PDGFRs expression in dogs affected by malignant oral melanomas: correlation with prognosis.

Canine malignant melanoma (CMM) is the most common canine oral tumour, and up to 70-75% of dogs in stage II-III die within 1 year after surgery. The purpose of this study was to evaluate the expression of platelet-derived growth factors receptors (PDGFR)-α and -ß in stage II and III CMMs and to correlate it with prognosis. PDGFRs expression was evaluated by immunohistochemistry on 48 cases of formalin-fixed CMM samples and correlated with clinical-pathological findings and outcome after surgery. PDGFRs co-expression was observed in 37.5% of cases. Positivity for PDGFR-α and -ß receptor was present in 54.2 and 47.9% of cases, respectively. Ki67 values >19.5% were ascertained in 66.7% of cases. Statistical analysis showed that PDGFRs co-expression and Ki67 values > 19.5% were both associated with worse prognosis. PDGFRs expression suggests a role in the pathogenesis and progression of CMM, and α and ß co-expression appears to be associated to worse prognosis.

Prolongation of survival of dogs with oral malignant melanoma treated by en bloc surgical resection and adjuvant CSPG4-antigen electrovaccination.

Reported post-surgery 1-year survival rate for oral canine malignant melanoma (cMM) is around 30%; novel treatments are needed as the role of adjuvant chemotherapy is unclear. This prospective study regards adjuvant electrovaccination with human chondroitin sulfate proteoglycan-4 (hCSPG4)-encoded plasmid in 23 dogs with resected II/III-staged CSPG4-positive oral cMM compared with 19 dogs with resected only II/III-staged CSPG4-positive oral cMM. Vaccination resulted in 6-, 12-, 18- and 24-month survival rate of 95.6, 73.9, 47.8 and 30.4%, respectively [median survival time (MST) 684 days, range 78-1694, 8 of 23 dogs alive] and 6-, 12-, 18- and 24-month disease-free interval (DFI) rate of 82.6, 47.8, 26.1 and 17.4%, respectively (DFI 477 days, range 50-1694). Non-vaccinated dogs showed 6-, 12-, 18- and 24-month survival rate of 63.2, 26.3, 15.8 and 5.3%, respectively (MST 200 days, range 75-1507, 1 of 19 dogs alive) and 6-, 12-, 18- and 24-month DFI rate of 52.6, 26.3, 10.5 and 5.3%, respectively (DFI 180 days, range 38-1250). Overall survival and DFI of vaccinated dogs was longer in those <20 kg. In vaccinated and non-vaccinated dogs local recurrence rate was 34.8 and 42%, respectively while lung metastatic rate was 39 and 79%, respectively.

Quantitative analysis of fetal DNA in maternal plasma in pathological conditions associated with placental abnormalities.

An increased fetal DNA concentration in maternal plasma has been observed in placental pathological conditions associated with hypertension and preeclampsia. To confirm these data, we performed real-time quantitative PCR on the SRY gene in a group of physiological and pathological male-bearing pregnancies. In 78 physiological pregnancies, fetal DNA concentration in maternal plasma was 20.7, 13.4, 23.6, and 74.8 genome-equivalents (g.e.)/mL during the first, second, and third trimesters and at term, respectively. In 10 preeclamptic women, fetal DNA concentration ranged from 59.3 to 615.2 g.e./mL (median: 332.9). In 7 women with preeclampsia and IUGR (intrauterine growth retardation), fetal DNA ranged from 96.5 to 859 g.e./mL (median: 146.8). In 4 women with IUGR and hypertension, fetal DNA ranged from 34 to 473.5 g.e./mL (median: 142.4). In 3 patients with IUGR, fetal DNA ranged from 168.6 to 519.7 g.e./mL (median: 308.1). In 2 patients with IUGR and HELLP (hemolysis, elevated liver enzymes, and low platelet count) syndrome, fetal DNA concentration ranged from 105 to 394.1 g.e./mL (median: 249.7). Four women who developed preeclampsia some weeks later showed fetal DNA levels within the physiological range. These data suggest that increased fetal DNA concentrations might represent a valuable marker of placental abnormalities and suggest that this rise may precede clinical manifestation of preeclampsia by only a few weeks.

[Traumatic lesions of the diaphragm]. / Lesioni traumatiche del diaframma.

The authors report their experience of 21 cases of post-traumatic hernias of the diaphragm. On the basis of the results obtained by discussion of etiologic, diagnostic and therapeutic patterns they make at the conclusion that the high mortality, associated with diaphragmatic hernias, can be reduced only with a short time of diagnosis and a prompt surgical treatment of the associated lesions.

[Varicocele: cause of sub-fertility (therapeutic considerations)]. / Varicocele: causa di sub-fertilità (considerazioni terapeutiche).

The Authors examined the seminal liquid of 60 patients suffering from non-obstructive oligosperma after different treatments. On the basis of the results obtained, they emphasize the importance, after operation, of the medical treatment in the normohormonal varicocelic patients. They suggest the surgical treatment in the non-varicocelic subjects, in who an inversion of the veenous flux in an inside spermatic vein was ascertained.

[Carnitine in postoperative parenteral treatment]. / La carnitina nel trattamento parenterale postoperatorio.

The Authors study the effect of intravenous L-Carnithine on the free plasma amino acid pattern in the post-operative course of a group of 25 selected patients who underwent toracic and abdominal elective surgical procedures. They compared the results with the data from another group of patients, in conditions similar to the former, but who did not receive Carnithine. The results show that Carnithine is able to reduce gluconeogenesis and proteolysis, probably by an improvement of lipolysis; so the Authors believe that Carnithine carries a useful contribution in the post-operative care of the surgical patient.

[Blood amino acid pattern in thyreopathic patients. (pre- and post-operative analysis)]. / Il pattern aminoacidemico in pazienti tireopatici. (Analisi pre- e post-operatoria).

On the basis of the effects, demonstrated in vitro, of the thyroid hormones on the amino-acidic metabolism at cellular level, the Authors analysed the aminoacidogram of 15 thyreopathic patients. They remarked significant preoperative modifications of some amino-acids, coming back to standard values after operation. The authors think the preoperative modifications are to be ascribed to thyreopathy, whereas the postoperative ones depend on the surgical trauma.

[Popliteal aneurysm (therapeutic considerations)]. / L'aneurisma popliteo (considerazioni terapeutiche).

The authors show a case of popliteal artery aneurysm they had the opportunity to observe. In consideration of the high percentage of surgical failures; recorded in the treatment of the complicate forms, they point out the importance of precocious diagnosis. The Authors think the termino-terminal arterial anastomosis after aneurysmectomy has very limited indications.

[Carotid paragangliomas]. / I paragangliomi carotidei.

Three cases of carotid body paragangliomas are reported. The authors underline the critical diagnostic role of carotid arteriogram whenever such disease is suspected. Surgical treatment can lead to good results even in malignant forms. In the latter, treatment should be completed with radiotherapy.

[Spontaneous pneumothorax: surgical aspects]. / Pneumotorace spontaneo: aspetti chirurgici.

The authors illustrate the cases of spontaneous pneumothorax observed in their institute along with the diagnostic and therapeutic aspects. In accord with the experience of others as reported in the literature, they stress the importance of a precise, immediate diagnosis for the purposes of adopting the treatment of choice: in the presence of closed, partial forms a conservative approach is to be preferred, whereas in open and/or hypertensive cases an aspirative thoracic drainage must be provided without delay. Aggressive surgical treatment, with resection of the bullous lesions responsible for bronchopleural fistulas, will resolve the condition and should be implemented after a reasonable waiting period with aspirative drainage, or even, electively, in the first instance, in the presence of multiple relapses. In any event, the authors stress the need to avoid uncertainty and delay in view of the youthful age of most of the subjects affected and the potential danger of the complications of this apparently banal disease.

[Primary lymphomas of the gastro-intestinal tract]. / I linfomi primitivi del tratto gastro-intestinale.

The authors considered a series of 13 patients undergone surgical operation for primary malignant lymphoma of digestive system, with gastric, gastro-jejunal, jejunal, ileal and colic localization. They examined diagnostic and therapeutic features and the follow-up data. According to literature, the authors remark the importance of roentgenology and endoscopy, that together with bioptic data may reach a definite and early diagnosis; an elective and wide surgical exeresis seems useful in early stages, showing a better prognosis and epithelial malignancies. IV stage patients, however, had a very poor survival; a quick management appears today the only factor affecting long-term results in these patients.

[Lyophilized amino acids versus solutions of crystallized amino acids in total parenteral nutrition]. / Aminoacidi liofilizzati versus soluzioni di aminoacidi cristallizzati nella nutrizione parenterale totale.

The authors considered the possibility, for purposes of total parenteral nutrition, to use lyophilized amino-acids as an alternative to the traditional amino-acid solutions, and resolved to check their nutritional and metabolic effectiveness. For this purpose, they appraised some parameters concerning the proteic metabolism in two homogeneous groups of surgical patients, subjected to T.P.N., one with crystallized amino-acids in solution and the other with lyophilized amino-acids. The supply in glucides and in lipides was identic in both groups. It appears evident from the results that the lyophilized amino-acids not only show the advantage of being administrable in nutritional mixtures with reduced volume, but also represent a valid plastic source, and can surely replace the traditional commercial amino-acid solutions.

[Anti-microsomal, anti-thyroglobulin antibodies and thyroid stimulants in hyperthyroid subjects. Analysis of 315 patients followed-up for 3 years at a single medical center]. / Anticorpi anti micrsomi, anti tireoglobulina e tiroido stimolanti in soggetti ipertiroidei. Analisi di 315 pazienti seguiti per tre anni presso un unico centro medico.

The objective of the study was to evaluate the significance of the determination of antithyroid antibodies in hyperthyroid patients. Two-hundred-fifteen untreated Graves' hyperthyroid patients (active toxic diffuse goiter-TDG), 54 Plummer's hyperthyroid patients (focal hyperthyroidism) and 46 subjects with other forms of hyperthyroidism were studied. Serum levels of T4, T3, TSH, TSH receptor antibody (TRAb), microsomal antibody (TMAb), and thyroglobulin antibody (TGAb) were evaluated before starting treatment, at regular intervals during therapy, and during the follow-up period after therapy was withdrawn. The antibodies were positive in all patients with active and non-active TGD but positive in only two patients (3.7%) with focal hyperthyroidism. During the treatment interval, TRAb, TMAb and TGAb serum levels fell with a nadir in the 7th month of therapy. In particular, TRAb fell to normal levels in all patients who had basal levels less than 500 U/l (97.7% of the cases) while TMAb and TGAb remained positive. Relapses, following the completion of therapy, occurred in 20.4% after one year and in 33% after two years. Relapses were always linked to a new increase in TRAb. In conclusion, TRAb can be useful in the determination of early disease and in diagnosing remission. It did not appear useful as a prognostic indicator for relapse in individual patients.

[Management of groin hernias: long term results]. / La chirurgia erniaria: esperienza pluriennale.

The Authors report their experience in the treatment of groin hernias. Over the years, hospital stay and anaesthetic procedure were modified without compromising the quality of results. The Authors conclude that groin hernia may be treated in a outpatient or day surgery regimen saving money.

Isolation, purification, culture and characterisation of myoepithelial cells from normal and neoplastic canine mammary glands using a magnetic-activated cell sorting separation system.

Mammary gland tumours, the most common malignant neoplasm in bitches, often display myoepithelial (ME) cell proliferation. The aim of this study was to isolate, purify, culture and characterise ME cells from normal and neoplastic canine mammary glands. Monodispersed cells from three normal canine mammary glands and five canine mammary tumours were incubated with an anti-Thy1 antibody and isolated by magnetic-activated cell sorting (MACS). Cells isolated from two normal glands (cell lines CmME-N1 and CmME-N2) and four tumours (cell lines CmME-K1 from a complex carcinoma, CmME-K2 from a simple tubulopapillary carcinoma, and CmME-K3 and CmME-K4 from two carcinomas within benign tumours) were cultured in supplemented DMEM/F12 media for 40days. Cell purity was >90%. Tumour-derived ME cell lines exhibited heterogeneous morphology, growth patterns and immunocytochemical expression of cytokeratins, whereas cell lines from normal glands retained their morphology and levels of cytokeratin expression during culture. Cell lines from normal glands and carcinomas within benign tumours grew more slowly than those from simple and complex carcinomas. This methodology has the potential to be used for in vitro analysis of the role of ME cells in the growth and progression of canine mammary tumours.