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Cancer-related pain represents one of the most common complaints of cancer patients especially for those with advanced-stage of disease and/or bone metastases. More effective therapeutic strategies are needed not only to improve the survival of cancer patients but also to relieve cancer-related pain. In the last decade, immune checkpoint inhibitor (ICI)-based immunotherapy targeting programmed cell death-1 (PD-1) and its ligand 1 (PD-L1) has revolutionized cancer care. Beyond its anticancer role, PD-1/PD-L1 axis pathway is involved in many other physiological processes. PD-L1 expression is found in both malignant tissues and normal tissues including the dorsal root ganglion, and spinal cord. Through its interaction with PD-1, PD-L1 can modulate neuron excitability, leading to the suppression of inflammatory, neuropathic, and bone cancer pain. Therefore, since the intricate relationship between immunotherapy and pain should be largely dissected, this comprehensive review explores the complex relationship between PD-1/PD-L1-based immunotherapy and cancer-related pain. It delves into the potential mechanisms through which PD-1/PD-L1 immunotherapy might modulate pain pathways, including neuroinflammation, neuromodulation, opioid mechanisms, and bone processes. Understanding these mechanisms is crucial for developing future research directions in order to optimize pain management strategies in cancer patients. Finally, this article discusses the role of artificial intelligence (AI) in advancing research and clinical practice in this context. AI-based strategies, such as analyzing large datasets and creating predictive models, can identify patterns and correlations between PD-1/PD-L1 immunotherapy and pain. These tools can assist healthcare providers in tailoring treatment plans and pain management strategies to individual patients, ultimately improving outcomes and quality of life for those undergoing PD-1/PD-L1-based immunotherapy.

Checkpoint inhibitors (ICIs) have demonstrated substantial efficacy in the treatment of numerous solid tumors, including head and neck cancer. Their inclusion in the therapeutic paradigm in metastatic lines of treatment has certainly improved the outcomes of these patients. Starting from this assumption, numerous studies have been conducted on ICIs in other earlier disease settings, including studies conducted in patients in neoadjuvant settings. However, how many and which studies are truly significant? Can they lay concrete foundations for further future studies and therefore allow us to continue to have this interesting future perspective? Through a review of the existing literature, coupled with insights gleaned from clinical practice and from the main recently published studies, we aim to examine the therapeutic potential of ICIs in patients affected by head and neck cancer in a neoadjuvant treatment setting and encourage researchers to set up successful future clinical trials.

IntroductionMany lactic acid bacteria (LAB) strains are currently gaining attention in the food industry and various biological applications because of their harmless and functional properties. Given the growing consumer demand for safe food, further research into potential probiotic bacteria is beneficial. Therefore, we aimed to characterize Pediococcus pentosaceus DSPZPP1, a LAB strain isolated from traditional fermented sausages from the Basilicata region of Southern Italy.MethodsIn this study, we analyzed the whole genome of the P. pentosaceus DSPZPP1 strain and performed in silico characterization to evaluate its applicability for probiotics and use in the food industry.Results and DiscussionThe whole-genome assembly and functional annotations revealed many interesting characteristics of the DSPZPP1 strain. Sequencing raw reads were assembled into a draft genome of size 1,891,398 bp, with a G + C content of 37.3%. Functional annotation identified 1930 protein-encoding genes and 58 RNAs including tRNA, tmRNA, and 16S, 23S, and 5S rRNAs. The analysis shows the presence of genes that encode water-soluble B-group vitamins such as biotin, folate, coenzyme A, and riboflavin. Furthermore, the analysis revealed that the DSPZPP1 strain can synthesize class II bacteriocin, penocin A, adding importance to the food industry for bio-enriched food. The DSPZPP1 genome does not show the presence of plasmids, and no genes associated with antimicrobial resistance and virulence were found. In addition, two intact bacteriophages were identified. Importantly, the lowest probability value in pathogenicity analysis indicates that this strain is non-pathogenic to humans. 16 s rRNA-based phylogenetic analysis and comparative analysis based on ANI and Tetra reveal that the DSPZPP1 strain shares the closest evolutionary relationship with P. pentosaceus DSM 20336 and other Pediococcus strains. Analysis of carbohydrate active enzymes (CAZymes) identified glycosyl transferases (GT) as a main class of enzymes followed by glycoside hydrolases (GH). Our study shows several interesting characteristics of the isolated DSPZPP1 strain from fermented Italian sausages, suggesting its potential use as a promising probiotic candidate and making it more appropriate for selection as a future additive in biopreservation.

We describe here a rare case of pilomatrix carcinoma in the right parotid region, arising in a young patient.Pilomatrix carcinoma is a rare, locally aggressive tumor with a tendency to recur. Pilomatrixoma is a superficial benign skin tumor arising from the matrix cells of the hair follicle generally located in the scalp, face, and upper limbs. Clinically, it usually presents as a solitary subcutaneous blue-black nodule which grows slowly.An 18-year-old male, non-smoker, in good health, was referred to our Unit after the onset of a swelling in the right parotid region. The lesion had been present for 1 year but the patient did not seek medical attention in that time. Clinical examination showed an exophytic mass in the right parotid region measuring 20 × 20 mm. An ultrasound of the major salivary glands showed an oval lesion of the right parotid gland; contrast-enhanced MRI appeared to show an oval lesion in the right intraparotid region, approximately 20 × 25 mm, which was hypointense in T1 images, and hyperintense in T2 images, with inhomogeneous contrast-enhancement; Fine Needle Aspiration Cytology (FNAC) was indicative of a lesion with high suspicion of malignancy.We elected to carry out a facial nerve sparing total parotidectomy, under general anesthesia, and facial reconstruction of the remaining gap with a sternocleidomastoid muscle flap. Histopathological analysis demonstrated basaloid cell proliferation beneath granulation tissue, hemorrhage, and large number of “ghost cells” with high mitotic activity. This confirmed the diagnosis of pilomatrix carcinoma. Postoperative outcome was uneventful.

Iatrogenic damage to the spinal accessory nerve is very common during surgical procedures in the neck region, especially during oncological surgery. An injury to this nerve can cause different deficiencies, from a poorly definable painful symptomatology of the shoulder to a motor deficit of the shoulder girdle due to a denervation of the trapezius muscle, a condition known as Shoulder Syndrome (SS). In literature it is reported that the presence of an accessory innervation of the trapezius muscle rising from the cervical plexus (C2–C4) can contribute to, and in some cases replace, the innervation of the trapezius muscle by the accessory nerve. In this study we show a case of a patient, who had undergone a radical neck dissection, who did not report a functional deficit of the shoulder, strengthening the hypothesis of a replacement innervation starting from the cervical plexus (C2–C4). It is therefore important to preserve this innervation during surgical procedures involving the neck due to the positive impact it would have on the patient's Quality of Life (QOL).

Our study aimed to evaluate the impact of the pipeline installation on the bacterial composition in cultivated soil by metagenomic analyses performed before the excavation and in the following three years. Differential abundance analysis was obtained using DESeq2 from the GAIA pipeline to verify the bacteriological diversity in soils collected after the reference year (2013). Soil samples presented a different distribution of taxa, especially in 2014, in which a further allocation at the phylum and family levels was observed compared to the previous year (2013). The phyla Bacteroidetes and Firmicutes increased significantly, while the phylum Actinobacteria, most abundant in 2013, showed reduced abundance; moreover, Chloroflexi and Planctomycetes decreased considerably, and Verrucomicrobia was absent. The significant differences in the taxonomic composition and structure of the soil microbial community were due to critical stress conditions following the soil excavations. The bacterial communities were capable of profound physiological and genetic changes, implementing different mechanisms for survival and adaptation to an environment with changed conditions. The implication of changes in microbial diversity before and after the mechanical insult of soil has been determined.

Recent reports on secondary restorations with subperiosteal implants have demonstrated promising results in terms of esthetic and functional restoration. We report the case of a reconstruction of a total maxillectomy with a custom-made subperiosteal implant associated with a temporal muscle flap in a patient who could not undergo bone reconstruction with a free flap. This technique made it possible to restore the division between the oral cavity and the mouth, providing a solid anchorage to the dental prosthesis and correcting an oroantral communication with a small palatal obturator. The subperiosteal implant also granted proper soft tissue support in the middle-third of the face. Subperiosteal implants can be safe and effective even in primary maxillary reconstructions for patients who cannot undergo free bone flap reconstructions. In these difficult cases, this type of implant can provide support to the soft tissues of the middle-third of the face and a solid anchorage for dental prostheses or palatal obturators, thus improving the quality of life for patients.

Abstract Background The lack of objective data makes it difficult to establish the prognostic value of chemosensitive disorders in coronavirus disease 2019 (COVID-19) patients. We aimed to prospectively monitor patients diagnosed with COVID-19 to see if the severity of olfactory and gustatory dysfunction associates with subsequent disease severity. Methods Multicentre prospective study that recruited 106 COVID-19 subjects at diagnosis. Chemosensitive functions were assessed with psychophysical tests within 4 days of clinical onset, at 10 and 20 days. Daily body temperature and oxygen saturation were recorded as markers of disease severity alongside need for hospitalisation. The correlation between olfactory and gustatory scores and disease severity was assessed with linear regression analysis. Results At T0, 71 patients (67%) presented with olfactory dysfunction while gustatory impairment was detected in 76 cases (65.6%). Chemosensitive disorders gradually improved over the observation period. No significant correlations were found between T0 chemosensitive scores and final disease severity. The correlation between olfactory scores and fever proved significant at T2 (p = 0.05), while the relationship with gustatory scores was significant at T1 (p = 0.01) and T2 (p

Abstract Background The anatomical complexity of the oropharynx and the difficulty in reaching its distal portion have always conditioned the surgical accessibility. Robotic surgery represents an excellent alternative in the treatment of cervico-facial oncological diseases. Methods This series comprises all patients managed for head and neck cancer by Trans Oral Robotic Surgery TORS. The staging assessment, including neck ultrasound and total body PET/CT scan, was performed in each patient according to the TNM classification. All charts were recorded with the following data: name and surname, age, gender, date of surgery intra or post-operative hemorragia, tumor site, histology, TNM stage, robot set-up time, tumor resection time, whether or not tracheotomy was performed, whether or not neck dissection was performed, insertion of a nasogastric tube or gastrostomy, time to resumption of oral feeding, surgical margins, mean length of hospital stay, adjuvant treatment and follow-up. Results From February 2013 to February 2018, TORS was performed in 67 consecutive patients affected by head and neck tumours. We divided, our sample, in 3 subsites: supraglottic larynx, parapharyngeal space and oropharynx. Pathology reports confimed malignancy in 44 cases: 8 cases lymphomas, 36 cases of Squamous cell carcinoma (SCC), 5 cases of benign salivary glands tumors and 18 miscellaneous cases. Neck dissection was performed in 12 cases. Tracheotomy was perfomed in 3/67 cases for respiratory failures. A nasogastric tube was inserted at the end of the surgical procedure in 21 patients. The mean length of hospital stay was 10 days . Major complications included post-operative bleeding in 3 patients, 1 exitus for massive bleeding 20 days post-surgery and 1 respiratory failure treated with tracheotomy and monitoring in the Intensive Care Unit (ICU) for 3 days. Conclusions Robotic surgery has been considered a valid alternative to traditional open treatment in many specializations with the advantages of an endoscopic procedure, with the same oncological and functional results and with fewer complications. The advantages of this type of surgical technique have been discussed, it is mandatory to focus on the indications and contraindications.

The Coronavirus disease 2019 (COVID-19) outbreak was declared by the World Health Organization (WHO) in March 2020 to be a pandemic and many drugs used at the beginning proved useless in fighting the infection. Lately, there has been approval of some new generation drugs for the clinical treatment of severe or critical COVID-19 infections. Nevertheless, more drugs are required to reduce the pandemic’s impact. Several treatment approaches for COVID-19 were employed since the beginning of the pandemic, such as immunomodulatory, antiviral, anti-inflammatory, antimicrobial agents, and again corticosteroids, angiotensin II receptor blockers, and bradykinin B2 receptor antagonists, but many of them were proven ineffective in targeting the virus. So, the identification of drugs to be used effectively for treatment of COVID-19 is strongly needed. It is aimed in this review to collect the information so far known about the COVID-19 studies and treatments. Moreover, the observations reported in this review about carbazoles as a treatment can signify a potentially useful clinical application; various drugs that can be introduced into the therapeutic equipment to fight COVID-19 or their molecules can be used as the basis for designing new antivirals.

Viral infections have always been one of the most frequent causes of persistent olfactory dysfunctions accounting for 18% to 45% of all cases [...]

The beginning of the end or the end of the beginning? After two years mastered by coronavirus disease 19 (COVID-19) pandemic, we are now witnessing a turnaround. The reduction of severe cases and deaths from COVID-19 led to increasing importance of a new disease called post-COVID syndrome. The term post-COVID is used to indicate permanency of symptoms in patients who have recovered from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Immune, antiviral, antimicrobial therapies, as well as ozone therapy have been used to treat COVID-19 disease. Vaccines have then become available and administered worldwide to prevent the insurgence of the disease. However, the pandemic is not over yet at all given the emergence of new omicron variants. New therapeutic strategies are urgently needed. In this view, great interest was found in nutraceutical products, including vitamins (C, D, and E), minerals (zinc), melatonin, probiotics, flavonoids (quercetin), and curcumin. This review summarizes the role of nutraceuticals in the prevention and/or treatment of COVID-19 disease and post-COVID syndrome.

In this study, we investigated whether treatment with palmitoylethanolamide and luteolin (PEA-LUT) leads to improvement in the quantitative or qualitative measures of olfactory dysfunction or relief from mental clouding in patients affected by long COVID. Patients with long COVID olfactory dysfunction were allocated to different groups based on the presence (“previously treated”) or absence (“naïve”) of prior exposure to olfactory training. Patients were then randomized to receive PEA-LUT alone or in combination with olfactory training. Olfactory function and memory were assessed at monthly intervals using self-report measures and quantitative thresholds. A total of 69 patients (43 women, 26 men) with an age average of 40.6 + 10.5 were recruited. PEA-LUT therapy was associated with a significant improvement in validated odor identification scores at the baseline versus each subsequent month; assessment at 3 months showed an average improvement of 10.7 + 2.6, CI 95%: 6–14 (p < 0.0001). The overall prevalence of parosmia was 79.7% (55 patients), with a significant improvement from the baseline to 3 months (p < 0.0001), namely in 31 patients from the Naïve 1 group (72%), 15 from the Naïve 2 group (93.7%), and 9 from the remaining group (90%). Overall, mental clouding was detected in 37.7% (26 subjects) of the cases, with a reduction in severity from the baseline to three months (p = 0.02), namely in 15 patients from the Naïve 1 group (34.8%), 7 from the Naïve 2 group (43.7%), and 4 from the remaining group (40%). Conclusions. In patients with long COVID and chronic olfactory loss, a regimen including oral PEA-LUT and olfactory training ameliorated olfactory dysfunction and memory. Further investigations are necessary to discern biomarkers, mechanisms, and long-term outcomes.

Head & Neck Osteomas are extremely rare osteogenic benign tumors, with unclear pathogenesis and heterogeneous clinical behavior. There are no studies in literature showing the characteristics of dimensional growth of such lesions. We report a case of a peripheral solitary osteoma of the sigmoid notch of the mandibular ramus, describing its radiographic growth in fourteen years. Measurements from OPTs (2003–6x7mm, 2008–8x12mm, 2014–17 × 24mm, 2016–19 × 25mm and 2017–21 × 28mm) and 3d cone-beam computed tomography scan (2016–19 × 15 × 21mm, 2017–21,4 × 19,2 × 22,7) were obtained. The growth of the lesion measured on OPTs was in mean 1.1 × 1.5 mm per year. This is the first case report in literature quantitatively assessing the growth of a solitary osteoma of the mandible through radiographic imaging, which seems to be more than 1 mm per dimension per year.

Accessory parotid gland (APG) is a small salivary gland tissue ranging from 0.5 to 1 cm diameter in size, located almost 7 mm anterior to the main parotid gland. APG is a common anatomical variant, but accessory parotid gland tumors are very rare, accounting for only 1%–7.7% of all parotid gland tumors. We present a case of adenoid cystic carcinoma involving accessory parotid gland, a very rare condition with only, to the best of our knowledge, other 7 cases described in literature. Surgical excision was performed and eventful postoperative recovery, without severe surgical complications and no signs of recurrence at 12 months of follow-up was obtained, with a good cosmetic result. An extensive review of the literature has been performed and the results are presented in order to establish a correct diagnostic-therapeutic protocol for these oncologic patients.

Objective: To predict the risk of metastatic lymph nodes and the tumor grading related to oral tongue squamous cell carcinoma (OTSCC) through the combination of clinical data with radiomics metrics by computed tomography, and to develop a supportive approach in the management of the lymphatic cervical areas, with particular attention to the early stages (T1−T2). Between March 2016 and February 2020, patients with histologically confirmed OTSCC, treated by partial glossectomy and ipsilateral laterocervical lymphadenectomy and subjected to computed tomography (CT) before surgery, were identified by two centers: 81 patients (49 female and 32 male) with 58 years as the median age (range 19–86 years). Univariate analysis with non-parametric tests and multivariate analysis with machine learning approaches were used. Clinical, hematological parameters and radiological features extracted by CT were considered individually and in combination. All clinical parameters showed statistically significant differences (p < 0.05) for the Kruskal−Wallis test when discriminating both the tumor grading and the metastatic lymph nodes. DOI, PLR, SII, and SIRI showed an accuracy of 0.70 (ROC analysis) when identifying the tumor grading, while an accuracy ≥ 0.78 was shown by DOI, NLR, PLR, SII, and SIRI when discriminating metastatic lymph nodes. In the context of the analysis of radiomics metrics, the original_glszm_HighGrayLevelZoneEmphasis feature was selected for identifying the tumor grading (accuracy of 0.70), while the wavelet_HHH_glrlm_LowGrayLevelRunEmphasis predictor was selected for determining metastatic lymph nodes (accuracy of 0.96). Remarkable findings were also obtained when classifying patients with a machine learning approach. Radiomics features alone can predict tumor grading with an accuracy of 0.76 using a logistic regression model, while an accuracy of 0.82 can be obtained by running a CART algorithm through a combination of three clinical parameters (SIRI, DOI, and PLR) with a radiomics feature (wavelet_LLL_glszm_SizeZoneNonUniformityNormalized). In the context of predicting metastatic lymph nodes, an accuracy of 0.94 was obtained using 15 radiomics features in a logistic regression model, while both CART and CIDT achieved an asymptotic accuracy value of 1.00 using only one radiomics feature. Radiomics features and clinical parameters have an important role in identifying tumor grading and metastatic lymph nodes. Machine learning approaches can be used as an easy-to-use tool to stratify patients with early-stage OTSCC, based on the identification of metastatic and non-metastatic lymph nodes.

Orthodontic tooth movement (OTM) is based on intermitted or continuous forces applied to teeth, changing the mechanical loading of the system and arousing a cellular response that leads to bone adaptation. The traditional orthodontic movement causes a remodeling of the alveolar bone and changes in the periodontal structures that lead to tooth movement. The use of a piezoelectric instrument in orthodontic surgery has already shown great advantages. The purpose of this study is to rank the behavior of inflammatory mediators in accelerating orthodontic tooth movement. Ten patients with malocclusion underwent orthodontic surgical treatment, which included a first stage of surgically guided orthodontic movement (monocortical tooth dislocation and ligament distraction, MTDLD) to accelerate orthodontic movements. In all cases, corticotomy was performed by Piezosurgery. Bone and dental biopsy was executed to evaluate changes in the cytokines IL-1beta, TNF-alpha and IL-2 in different time intervals (1, 2, 7, 14 and 28 days). The molecular mediators are IL-1 beta, TNF-alpha and IL-2. Immediately after the surgical procedure there was a mild expression of the three molecular markers, while the assertion of IL-1 beta and TNF-alpha reached the maximum value after 24 h and 48 h, indicating a strong activation of the treated tissues. The Piezosurgery® surgical technique induces an evident stress in short times, within 24–48 h from the treatment, but it decreases significantly during the follow-up.

(1) Background: Persistent olfactory (POD) and gustatory (PGD) dysfunctions are one of the most frequent symptoms of long-Coronavirus Disease 2019 but their effect on the quality of life (QoL) of patients is still largely unexplored. (2) Methods: An online survey was administered to individuals who reported to have had SARS-CoV-2 infection at least 6 months prior with persisting COVID-19 symptoms (using the COVID symptom index), including ratings of POD and PGD, and their physical (PCS) and mental (MCS) components of quality of life were assessed using the standardized short form 12 questionnaire (SF-12). (3) Results: Responses from 431 unique individuals were included in the analyses. The most frequent persistent symptoms were: fatigue (185 cases, 42.9%), olfactory dysfunction (127 cases, 29.5%), gustatory dysfunction (96 cases, 22.3%) and muscle pain (83 cases, 19.3%). Respondents who reported persisting muscle pain, joint pain, fatigue, headache, gastrointestinal disturbances, and dyspnea had significantly worse PCS. Those experiencing persistent fatigue and dyspnea also showed significantly lower MCS. Respondents reporting POD or PGD showed significantly worse QoL, but only pertaining to the MCS. Multiple regressions predicted MCS based on olfactory and marginally on gustatory ratings, but not PCS. Age significantly affected the prediction of PCS but not MCS, and gender and temporal distance from the COVID-19 diagnosis had no effect. (4) Conclusions: POD and PGD are frequent symptoms of the long-COVID-19 syndrome and significantly reduce QoL, specifically in the mental health component. This evidence should stimulate the establishment of appropriate infrastructure to support individuals with persistent CD, while research on effective therapies scales up.

Myoepithelial carcinoma (MC), also known as malignant myoepithelioma, shows an infiltrative and destructive growth [1]. Myoepithelial neoplasms account for about 1.5% of all salivary tumors, and MC is even more rare, representing about 10% of myoepitheliomas [1–3] with a reported incidence of 0.2% of all salivary gland tumors. In this case, the cytological diagnosis (pleomorphic adenoma) and negative lymph nodes, addressed the surgeon for a parotidectomy, following guidelines and literature [27]. The best treatment for huge, relapsing tumors, notwithstanding cytological diagnosis, is not only parotidectomy, as lymphadenectomy should be performed too, given myoepithelial carcinoma's high-grade potential and unpredictable biologic behavior. Careful patient follow-up and staging, is therefore essential for better characterization and understanding of this tumor's behavior in the future. We also considered a more conservative treatment following guidelines, as this case was lacking metastases and lymphatic involvement, considering that application of guidelines, surgical and clinical expertise and appropriate technology can contain potential medicolegal implications [28].

Sinonasal mucosal melanoma is a rare and highly aggressive tumour. This tumour often carries a poor prognosis because of local invasion and early distant metastasis. It's, in fact, an aggressive, fortunately rare, disease. It's more common among population in their seventies, with a prolonged course due to innocuous symptoms. We report a case of sinonasal mucosal melanoma in a 56-years old male who presented with a brownish sinonasal mass involving right nasal fossa, swelling and spontaneous epistaxis. We report this case for the one-time reconstruction treatment performed by our team.

In recent years, the phenomenon of antibiotic resistance in hospitals, communities and the environment has increasingly grown, so antibiotic resistance has become an urgent problem that requires a decisive and global intervention. Incorrect/unnecessary use of antibiotics contributes to increase the ability of microorganisms to develop resistance faster and faster. Research efforts must, therefore, be made to ensure a future in which antibiotic drugs will still be useful in combating infectious diseases. The search for new antibacterial compounds is fundamental. In this study, the antimicrobial activity of the compounds was evaluated against selected bacterial strains from food and environmental matrices by using the Agar Well Diffusion Assay. A total of thirty-six Gram-positive and Gram-negative bacteria were employed to determine the action spectrum and the antimicrobial effectiveness of a small series of thiourea derivatives. Results showed that the highest activities were found for compounds 1 and 4. The important role of the alkyl chain length and/or guanidine moiety in the width of action spectrum was evidenced. Further studies will allow evaluating the efficacy of the inhibiting action and the molecular mechanisms underlying this activity in order to identify compounds capable of counteracting the phenomenon of antibiotic resistance and to identify possible future applications of these newly synthesized compounds that have shown a high bactericidal action potential.

The carbazole class is made up of heterocyclically structured compounds first isolated from coal tar. Their structural motif is preponderant in different synthetic materials and naturally occurring alkaloids extracted from the taxonomically related higher plants of the genus Murraya, Glycosmis, and Clausena from the Rutaceae family. Concerning the biological activity of these compounds, many research groups have assessed their antiproliferative action of carbazoles on different types of tumoral cells, such as breast, cervical, ovarian, hepatic, oral cavity, and small-cell lung cancer, and underlined their potential effects against psoriasis. One of the principal mechanisms likely involved in these effects is the ability of carbazoles to target the JAK/STATs pathway, considered essential for cell differentiation, proliferation, development, apoptosis, and inflammation. In this review, we report the studies carried out, over the years, useful to synthesize compounds with carbazole moiety designed to target these kinds of kinases.

Background: The objective of this study was to investigate the efficacy and safety of early administration of oral corticosteroids (OC) or nasal corticosteroids (NC) as an add-on to olfactory training (OT) versus OT alone in patients with olfactory dysfunction (OD) related to coronavirus disease 2019 (COVID-19). Methods: Patients with a positive diagnosis of COVID-19 and OD were prospectively recruited from March 22 to December 15, 2020 from 4 European hospitals. Patients had confirmed OD on psychophysical testing. All patients undertook OT, with add-on 10 days of OC (group 1: OC + OT), or 1 month of NC (group 2: NC + OT) or olfactory training alone (group 3: OT). Olfactory evaluations (Sniffin’Sticks tests) were carried out at the time of inclusion, 1 and 2 months after the start of the therapeutic course. Results: A total of 152 hyposmic or anosmic patients completed the study. Group 1, 2 and 3 included 59, 22 and 71 patients, respectively and all patient groups were comparable regarding baseline Sniffin’Sticks tests. The median Sniffin’Sticks test values significantly improved from pre- to post-intervention in all groups. The increase of Sniffin’Sticks test values was higher in group 1 (OC + OT) compared with groups 2 and 3 (p < 0.001) at one month after treatment but did not remain so at 2 months. Groups 1, 2 and 3, respectively, presented parosmia in 20/71 (28.2%), 9/22 (40.9%) and 42/71 (59.2%) patients. This difference was statistically significant between group 1 and 3 (p < 0.001). There were no patients with a worsening of the disease or an increase of the severity of the COVID-19 symptoms. Conclusions: The use of OCs in patients with OD related to mild COVID-19 is generally well-tolerated without any case of deterioration of symptoms. OC is associated with greater improvement in psychophysical olfactory evaluations at 1-month post-treatment but there was no difference at 2 months. Parosmia may be reduced following treatment with OC and NC. On the basis of these preliminary results, it is possible to state that considering the 2 months efficacy of OC and NC with respect to the OT alone and the risk-benefit ratio, the benefit to start a specific treatment of COVID-19 related OD cannot be demonstrated and there is a need for a randomised controlled trial to assess this further.

Background: The first applications of computer-aided design/computer-aided manufacturing (CAD/CAM) in maxillofacial surgery date back to the 1980s. Since then, virtual surgical planning (VSP) has undergone significant development and is now routinely used in daily practice. Indeed, in an extraordinary period, such as that of the current COVID-19 pandemic, it offers a valuable tool in relation to the protection of healthcare workers. In this paper we provide a comprehensive summary of the clinical applications reported in the literature and review our experience using an in-house rapid prototyping technique in the field of maxillofacial surgery. methods: Our research was focused on reconstructive surgery, traumatology (especially in relation to orbital floor and zygomatic arch fractures), and COVID-19 masks. The first step was a radiographic study. Next, computed tomography (CT) scans were segmented in order to obtain a three-dimensional (3D) model. Finally, in the editing phase, through the use of specific software, a customized device for each patient was designed and printed. results: Four reconstructive procedures were performed with a perfect fitting of the surgical device produced by means of VSP. In nine orbital floor fracture cases a good overlapping of the mesh on the orbital floor was obtained. In sixteen zygomatic arch cases the post-operative CT scan showed an excellent fitting of the device and a correct fracture reduction. Regarding the COVID-19 period, six masks and shields produced proved to provide effective protection. conclusions: The timescale and costs required for the production of our “home-made” virtual design are low, which makes this method applicable to a large number of cases, for both ordinary and extraordinary activities.

Background: The objective evaluation of the olfactory function of coronavirus disease 2019 patients is difficult because of logistical and operator-safety problems. For this reason, in the literature, the data obtained from psychophysical tests are few and based on small case series. Methods: A multicenter, cohort study conducted in seven European hospitals between March 22 and August 20, 2020. The Sniffin-Sticks test and the Connecticut Chemosensory Clinical Research Center orthonasal olfaction test were used to objectively evaluate the olfactory function. Results: This study included 774 patients, of these 481 (62.1%) presented olfactory dysfunction (OD): 280 were hyposmic and 201 were anosmic. There was a significant difference between self-reported anosmia/hyposmia and psychophysical test results (p = 0.006). Patients with gastroesophageal disorders reported a significantly higher probability of presenting hyposmia (OR 1.86; p = 0.015) and anosmia (OR 2.425; p < 0.001). Fever, chest pain, and phlegm significantly increased the likelihood of having hyposmia but not anosmia or an olfactory disturbance. In contrast, patients with dyspnea, dysphonia, and severe-to-critical COVID-19 were significantly more likely to have no anosmia, while these symptoms had no effect on the risk of developing hyposmia or an OD. Conclusions: Psychophysical assessment represents a significantly more accurate assessment tool for olfactory function than patient self-reported clinical outcomes. Olfactory disturbances appear to be largely independent from the epidemiological and clinical characteristics of the patients. The non-association with rhinitis symptoms and the high prevalence as a presenting symptom make olfactory disturbances an important symptom in the differential diagnosis between COVID-19 and common flu.

The prevalence of reactive nasal inflammatory conditions, for example, allergic rhinitis and chronic rhinosinusitis, is steadily increasing in parallel with significant environmental changes worldwide. Allergens and as yet undefined environmental agents may trigger these conditions via the involvement of host intrinsic factors, including the innate and adaptive immune system, the nasal epithelium, and the nasal nervous system. The critical role of the nasal microbiota in coordinating these components has emerged in recent studies documenting a significant association between microbial composition and the onset and progression of allergic or nonallergic inflammation. It is now clear that the local microbiota is a major player in the development of the mucosa-associated lymphoid tissue and in the regulation of such adaptive responses as IgA production and the function of effector and regulatory T cells. Microbial components also play a major role in the regulation of epithelial barrier functions, including mucus production and the control of paracellular transport across tight junctions. Bacterial components, including lipopolysaccharide, have also been shown to induce or amplify neuroinflammatory responses by engaging specific nociceptors. Finally, bacterial products may promote tissue remodeling processes, including nasal polyp formation, by interacting with formyl peptide receptors and inducing the expression of angiogenic factors and matrix-degrading enzymes.