Pembrolizumab-based first-line treatment for PD-L1-positive, recurrent or metastatic head and neck squamous cell carcinoma: a retrospective analysis.

BACKGROUND: The KEYNOTE-048 trial showed that pembrolizumab-based first-line treatment for R/M HNSCC led to improved OS in the PD-L1 CPS ≥ 1 population when compared to the EXTREME regimen. However, the R/M HNSCC real-world population is generally frailer, often presenting with multiple comorbidities, worse performance status and older age than the population included in phase III clinical trials. METHODS: This is a retrospective, single-centre analysis of patients with R/M HNSCC treated with pembrolizumab-based first-line treatment. RESULTS: From February 2021 to March 2023, 92 patients were treated with pembrolizumab-based first-line treatment. Patients treated with pembrolizumab-based chemoimmunotherapy had better ECOG PS and younger age than those treated with pembrolizumab monotherapy. Median PFS and OS were 4 months and 8 months, respectively. PFS was similar among patients treated with pembrolizumab-based chemoimmunotherapy and pembrolizumab monotherapy, while patients treated with pembrolizumab monotherapy had worse OS (log-rank p =.001, HR 2.7). PFS and OS were improved in patients with PD-L1 CPS > = 20 (PFS: log-rank p =.005, HR 0.50; OS: log-rank p =.04, HR 0.57). Patients with higher ECOG PS scores had worse PFS and OS (PFS, log-rank p =.004; OS, log-rank p = 6e-04). In multivariable analysis, ECOG PS2 was associated with worse PFS and OS. CONCLUSIONS: PFS in our real-world cohort was similar to the KEYNOTE-048 reference while OS was numerically inferior. A deeper understanding of clinical variables that might affect survival outcomes of patients with R/M HNSCC beyond ECOG PS and PD-L1 CPS is urgently needed.

A new 3D-printed temporal bone: 'the SAPIENS'-specific anatomical printed-3D-model in education and new surgical simulations.

PURPOSE: Otology and neuro-otology surgeries pose significant challenges due to the intricate and variable anatomy of the temporal bone (TB), requiring extensive training. In the last years 3D-printed temporal bone models for otological dissection are becoming increasingly popular. In this study, we presented a new 3D-printed temporal bone model named 'SAPIENS', tailored for educational and surgical simulation purposes. METHODS: The 'SAPIENS' model was a collaborative effort involving a multidisciplinary team, including radiologists, software engineers, ENT specialists, and 3D-printing experts. The development process spanned from June 2022 to October 2023 at the Department of Sense Organs, Sapienza University of Rome. Acquisition of human temporal bone images; temporal bone rendering; 3D-printing; post-printing phase; 3D-printed temporal bone model dissection and validation. RESULTS: The 'SAPIENS' 3D-printed temporal bone model demonstrated a high level of anatomical accuracy, resembling the human temporal bone in both middle and inner ear anatomy. The questionnaire-based assessment by five experienced ENT surgeons yielded an average total score of 49.4 ± 1.8 out of 61, indicating a model highly similar to the human TB for both anatomy and dissection. Specific areas of excellence included external contour, sigmoid sinus contour, cortical mastoidectomy simulation, and its utility as a surgical practice simulator. CONCLUSION: We have designed and developed a 3D model of the temporal bone that closely resembles the human temporal bone. This model enables the surgical dissection of the middle ear and mastoid with an excellent degree of similarity to the dissection performed on cadaveric temporal bones.

What the urologist needs to know before radical prostatectomy: MRI effective support to pre-surgery planning.

BACKGROUND: Radical prostatectomy (RP) is recommended in case of localized or locally advanced prostate cancer (PCa), but it can lead to side effects, including urinary incontinence (UI) and erectile dysfunction (ED). Magnetic resonance imaging (MRI) is recommended for PCa diagnosis and staging, but it can also improve preoperative risk-stratification. PURPOSE: This nonsystematic review aims to provide an overview on factors involved in RP side effects, highlighting anatomical and pathological aspects that could be included in a structured report. EVIDENCE SYNTHESIS: Considering UI evaluation, MR can investigate membranous urethra length (MUL), prostate volume, the urethral sphincter complex, and the presence of prostate median lobe. Longer MUL measurement based on MRI is linked to a higher likelihood of achieving continence restoration. For ED assessment, MRI and diffusion tensor imaging identify the neurovascular bundle and they can aid in surgery planning. Finally, MRI can precisely describe extra-prostatic extension, prostate apex characteristics and lymph-node involvement, providing valuable preoperative information for PCa treatment. CONCLUSIONS: Anatomical principals structures involved in RP side effects can be assessed with MR. A standardized MR report detailing these structures could assist urologists in planning optimal and tailored surgical techniques, reducing complications, and improving patients' care.

The Medical Historical Cultural Foundations of Western Nasal Surgery from Ancient Greece to the Middle Ages.

The manuscript aims to clarify the origins of Western rhinosurgery through the ancient texts of the greatest physicians of the past, up to the Byzantine Era, focusing on the "exchange of knowledge" between peoples. This excursus is carried out by quoting the texts of the greatest doctors of the past, such as Hippocrates, Galen and Celsus and by analysing the works of Byzantine authors such as Oribasius, Aetius, Antillus, which, more than others, represent the moment of fusion and interpenetration of Ancient Medical knowledge, paving the way for the Medieval Scholae Medicae in the West. The aim, therefore, is to fill that sort of "great gap" (from the foundation of Constantinople in the 4th century AD to the early Arab culture in the 11th century AD) due to the fact that figures such as Branca, Vianeo and, finally, Tagliacozzi, are considered direct actors of a recovery of the "ancient knowledge" of classic authors. This literature tends to less evaluate, instead, that important and huge cultural exchange -literally osmotic- in medical and surgical knowledge between peoples and civilizations, that find a trait d'union in the application of medical knowledge and surgical practical techniques matured in the Byzantine, Arab and Early Medieval period. In final analysis, through the History of Rhinosurgery, this paper aims to highlight how Western medical knowledge is made up of the ensemble of cultures which are apparently distant and different from each other, which merge themselves in a truly universal and transcultural knowledge: the Medical knowledge. LEVEL OF EVIDENCE V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

US-Elastography for Breast Lesion Characterization: Prospective Comparison of US BIRADS, Strain Elastography and Shear wave Elastography.

PURPOSE: To evaluate the diagnostic performance of strain elastography (SE) and 2 D shear wave elastography (SWE) and SE/SWE combination in comparison with conventional multiparametric ultrasound (US) with respect to improving BI-RADS classification results and differentiating benign and malignant breast lesions using a qualitative and quantitative assessment. MATERIALS AND METHODS: In this prospective study, 130 histologically proven breast masses were evaluated with baseline US, color Doppler ultrasound (CDUS), SE and SWE (Toshiba Aplio 500 with a 7-15 MHz wide-band linear transducer). Each lesion was classified according to the BIRADS lexicon by evaluating the size, the B-mode and color Doppler features, the SE qualitative (point color scale) and SE semi-quantitative (strain ratio) methods, and quantitative SWE. Histological results were compared with BIRADS, strain ratio (SR) and shear wave elastography (SWE) all performed by one investigator blinded to the clinical examination and mammographic results at the time of the US examination. The area under the ROC curve (AUC) was calculated to evaluate the diagnostic performance of B-mode US, SE, SWE, and their combination. RESULTS: Histological examination revealed 47 benign and 83 malignant breast lesions. The accuracy of SR was statistically significantly higher than SWE (sensitivity, specificity and AUC were 89.2 %, 76.6 % and 0.83 for SR and 72.3 %, 66.0 % and 0.69 for SWE, respectively, p = 0.003) but not higher than B-mode US (B-mode US sensitivity, specificity and AUC were 85.5 %, 78.8 %, 0.821, respectively, p = 1.000). CONCLUSION: Our experience suggests that conventional US in combination with both SE and SWE is a valid tool that can be useful in the clinical setting, can improve BIRADS category assessment and may help in the differentiation of benign from malignant breast lesions, with SE having higher accuracy than SWE.

Loop characteristics and audio-vestibular symptoms or hemifacial spasm: is there a correlation? A multiplanar MRI study.

AIM: We investigated if loop characteristics correlate with audio-vestibular symptoms or hemifacial spasm in patients with a vascular loop in the root entry zone (VII and VIII) and in the internal auditory canal. MATERIALS AND METHODS: A retrospective, multicenter study analyzed 2622 consecutive magnetic resonance imaging (MRI) scans of the cerebellopontine angle of patients with asymmetric audio-vestibular symptom or hemifacial spasm; patients' symptoms were confirmed by clinical tests. MRIs displaying vascular loops visible in the axial view were analyzed using multiplanar reconstruction. We evaluated (1) depth of penetration of the loop into the internal auditory canal (IAC); (2) largest diameter of the vessel; (3) nerve(s) involved in the vascular impingement, position of the loop relative to such nerve(s) and number of contacts between vessel and nerve(s); (4) length of such contact. The loop metrics described above were correlated with the patients' audio-vestibular symptoms and hemifacial spasm. RESULTS: Three hundred ninety-nine patients displayed a loop visible in the MRI axial view and out of them only 118 displayed a direct contact between loop and nerve. The cochlear nerve was involved in a contact in 57.7%. Loops in direct nerve contact had a calibre > 0.85 mm, were located in the middle portion of the IAC, and correlated with vertigo (p = 0.002), tinnitus (p = 0.003), and hemifacial spasm (p < 0.001). Asymmetric sensorineural hearing loss (SNHL) correlated with number of contacts (p < 0.001) and length of contact (p < 0.05). The contact was asymptomatic in 41.5% of patients. CONCLUSION: Loop characteristics may help predict whether a vascular impingement is responsible for a symptom and guide the physician to select the best treatment. KEY POINTS: • A vascular loop in the internal auditory canal was observed in 18-20% of the patients in this study; whether a loop can be responsible for a compressive syndrome is still unclear in particular referred to the vestibulocochlear nerve. • Compression by a loop on the facial nerve causes hemifacial spasm; compression by a loop on the cochlear or vestibular nerve may cause audio-vestibular symptoms. • In patients with a loop, the loop calibre, the loop position, and the number of loop-nerve(s) assessed via the multiplanar MRI reconstruction technique may help assess whether the patient will manifest audio-vestibular symptoms or hemifacial spasm.

The impact of white matter hyperintensities on speech perception.

BACKGROUND: The presence of white matter hyperintensities (WMHs) can impact on normal brain function by altering normal signal transmission and determining different symptoms. AIM: To evaluate the relationship between the presence of brain WMHs and the scores of speech perception test (SPT) in a sample of normal-hearing patients under 70 years of age. MATERIAL AND METHOD: Prospective study. One hundred eleven patients underwent audiological screening with pure tone audiometry (PTA), tympanometry, speech perception testing (SPT), and brain magnetic resonance imaging (MRI). T2 sequences were analyzed to identify the presence of WMH that, if identified, were scored using the Fazekas score. Statistical multiple regression analysis was performed to understand the relationship between PTA and SPT score; the Pearson's and Spearman's tests were used to evaluate the correlation between Fazekas scores and SPT. Chi-square test was used to analyze the difference between gender. RESULTS: The results of PTA were not predictive of the SPT score. A negative statistically significant correlation (Spearman's, p = 0.0001; Pearson's, p < 0.001) was identified between the Fazekas score and the results of SPT. No statistically significant differences were identified in the correlation of WMH and SPT between males and females. CONCLUSION: Multiple WMHs in the brain can worsen word recognition in patients with normal auditory threshold; this may be related to the impact that these lesions have on the memory ability. Spread of lesions into the brain might reduce the brain capacity to remember words, despite the sound is correctly perceived by the ear.

Public hygiene and funeral rituals during the Risorgimento: mummies and ashes.

Starting in 1865, regulations pursuant to public hygiene issued by the Unitary Government provided for administrative and political control of the funerary practice. Specifically, they regulated the management of cemeteries and the burials, increasingly drawing the funeral rituals from the control of the Church and of Catholicism, therefore secularising death for the construction of a new political religion. Hygiene became fundamental in order to promulgate cremation as a system of preserving the integrity of the bodies, preserving the ashes as a tangible and indestructible product of body matter and as a measure to protect public health by eliminating the risk of miasmatic pollution of the air caused by the cadaveric fumes. In the early 1870s, the practice of cremation began to spread, especially in the territories of Lombardy-Veneto and Savoy, as an expression of the progressive policies of the new Italian state, antagonistic to the old Catholic religious traditions. This paper intends to highlight the key aspects of the political significance that the cremation took on during the Risorgimento period, while also illustrating the methods adopted by important authors from that time period regarding incineration techniques and cremation methods.

Recovery of smell sense loss by mepolizumab in a patient allergic to Dermatophagoides and affected by chronic rhinosinusitis with nasal polyps.

BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) frequently presents with dysfunction or loss of the sense of smell, resulting in a significant impairment in quality of life. The medical treatments currently available may improve the olfactory function in patients with CRSwNP, but such an outcome is generally only transitory. We report the case of a patient with CRSwNP who completely recovered from smell sense loss by treatment with mepolizumab. CASE PRESENTATION: The patient was a 62-year-old female who has severe asthma induced by allergy to Dermatophagoides and concomitant CRSwNP. Any treatment for the latter, including oral and injective corticosteroids, was unsuccessful in the loss of smell. Due to the satisfaction of admission criteria to mepolizumab treatment for severe asthma, treatment was initiated on March 2018, resulting in good clinical control of both asthma and CRSwNP, and particularly in complete recovery of the smell loss after 4 months of treatment and still persisting. CONCLUSION: In this case report, the treatment with mepolizumab in a patient allergic to Dermatophagoides and affected by CRSwNP was associated with an improvement of anosmia. That finding may be explained by a reduction of the nasal obstruction by nasal polyps.

A Rare Case of Complete-Immunotherapy-Responsive Metastatic Non-Small Cell Lung Cancer with Long Lasting Progression-Free Survival: A Case Report.

BACKGROUND AND INTRODUCTION: Lung cancer is a prevalent and deadly disease globally. Non-small cell lung cancer (NSCLC) is the most common subtype, comprising 85% of cases. CASE REPORT: A 65-year-old male ex-smoker presented to our facility with a nocturnal cough. Various investigations revealed that he had metastatic NSCLC, for which he underwent chemotherapy with cisplatin and gemcitabine, followed by immunotherapy with Nivolumab. He achieved a complete response to the therapy and has remained free from recurrence for over 7 years since the initial diagnosis. DISCUSSION AND CONCLUSIONS: The treatment of metastatic NSCLC remains a significant therapeutic challenge, but the implementation of new therapeutic techniques has expanded the possibilities of achieving complete and durable eradication of the disease.

The role of CD73 in predicting the response to immunotherapy in head and neck cancer patients.

Immunotherapy has a crucial role in the treatment of recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC). However, only a small percentage of patients achieve long-term benefit in terms of overall response and survival. It was shown that HNSCC has an immunosuppressive microenvironment due to high levels of regulatory T cells and immunosuppressive molecules, such as LAG3 and CD73. The aim of our study was to investigate if the expression of CD73 by neoplastic and immune cells could affect the efficacy of anti-PD-1 immunotherapy. We reviewed data from 50 patients with R/M HNSCC receiving first line immunotherapy with or without chemotherapy based on a combined positive score (CPS). CD73 expression by cancer and immune cells was evaluated on pre-treatment and the percentage of stained cells was recorded. We analysed the association between CD73 expression on neoplastic and immune cells and early progression (EP), defined as progression occurring within 3 months. In 88 % of patients the primary tumour site was in the oral cavity or larynx. All patients received pembrolizumab associated in 40 % of cases to chemotherapy. CD73 was positive in 82 % and 96 % of cases on neoplastic and immune cells, respectively. The median value of CD73 was 32 % for neoplastic cells and 10 % for the immune ones. We observed a significant association between the CD73 expression on neoplastic cells over the median value and EP disease. We didn't record a correlation between the expression of CD73 on immune cells and early progression. Our findings suggest that higher expression of CD73 on neoplastic cells could predict resistance to immunotherapy in patients with CPS positive R/M HNSCC. The addition of this biomarker to routine evaluation of CPS could help to select the patients primary resistant to anti-PD-1 immunotherapy.

The Impact of the COVID-19 Pandemic on the Prognosis of Laryngeal Adenoid Cystic Carcinoma: A Case Report and a Literature Review.

Laryngeal adenoid cystic carcinoma (LACC) is a sporadic neoplasm, especially if supraglottic. The COVID-19 pandemic worsened the presenting stage of many cancers and impacted their prognosis negatively. Here, a case of a patient with adenoid cystic carcinoma (ACC) with delayed diagnosis and a rapid deterioration with distant metastasis due to the COVID-19 pandemic is illustrated. Next, we present a literature review of this rare glottic ACC. The COVID-19 pandemic worsened the stage of presentation of many cancers and adversely affected their prognosis. The present case had a rapidly lethal course, undoubtedly due to the diagnosis delay caused by the COVID-19 pandemic, which impacted the prognosis of this rare glottic ACC. Strict follow-up is recommended for any suspicious clinical findings, as an early diagnosis will improve the disease prognosis, and to consider the influence of the COVID-19 pandemic, especially on the timing of common diagnostic and therapeutic procedures for oncological diseases. In the post-COVID-19 era, it is important to generate new diagnostic scenarios to achieve an increasingly rapid diagnosis of oncological diseases, especially the rare ones, through screening or similar procedures.

Neuroinflammatory disorders of the brain and inner ear: a systematic review of auditory function in patients with migraine, multiple sclerosis, and neurodegeneration to support the idea of an innovative 'window of discovery'.

Background: Hearing can be impaired in many neurological conditions and can even represent a forme fruste of specific disorders. Auditory function can be measured by either subjective or objective tests. Objective tests are more useful in identifying which auditory pathway (superior or inferior) is most affected by disease. The inner ear's perilymphatic fluid communicates with the cerebrospinal fluid (CSF) via the cochlear aqueduct representing a window from which pathological changes in the contents of the CSF due to brain inflammation could, therefore, spread to and cause inflammation in the inner ear, damaging inner hair cells and leading to hearing impairment identifiable on tests of auditory function. Methods: A systematic review of the literature was performed, searching for papers with case-control studies that analyzed the hearing and migraine function in patients with neuro-inflammatory, neurodegenerative disorders. With data extracted from these papers, the risk of patients with neurological distortion product otoacoustic emission (DPOAE) was then calculated. Results: Patients with neurological disorders (headache, Parkinson's disease, and multiple sclerosis) had a higher risk of having peripheral auditory deficits when compared to healthy individuals. Conclusion: Existing data lend credence to the hypothesis that inflammatory mediators transmitted via fluid exchange across this communication window, thereby represents a key pathobiological mechanism capable of culminating in hearing disturbances associated with neuroimmunological and neuroinflammatory disorders of the nervous system.

Audiological and radiological characteristics of a family with T961G mitochondrial mutation.

OBJECTIVE: The aim of this study was to describe audiological and radiological characteristics, and other secondary aspects, in a family carrying a T961G mutation in the 12S rRNA mitochondrial gene. DESIGN: Case report. STUDY SAMPLE: Six members of a family participated in an audiological evaluation that included pure-tone audiometry, immittance tests, auditory brainstem responses (ABR), and otoacoustic emissions (OAE). The radiological evaluation was conducted through temporal bone CT scans using a Toshiba 16 channels Aquilon Spirale. Neuropsychiatric evaluation was also administered. RESULTS: Three participants were diagnosed with severe sensorineural hearing loss of cochlear origin and cochlear malformations visible in CT scans. One participant had a mild mixed-hearing loss and no cochlear malformations. Two participants had normal audiological and radiological findings. CONCLUSIONS: We believe our study can provide helpful insight on the clinical findings of a rare mutation, of which few data have been presented in literature.

THE ORIGINS OF THE BLOOD TRANSFUSION: EUROPEAN LITERATURE AND ITALIAN DEBATE ON NEW INNOVATIONS (1667-1668)

This paper deals with the literary debate on the first experiments regarding blood transfusion on human beings between 1667 and 1668 in Europe, with particular attention to the less-known experimental research, carried out in Italy. The authors examine the details of the experimental developments, focusing on the techniques and instruments used by physicians involved in this new surgical approach, with special attention to the Italian debate and experimentations. The article suggests that transfusion was considered a part of what we could call "emergency surgery". In this framework, Italian transfusional pioneers played a central role in the improvement and transmission of a discipline that was still in its dawning throughout Europe. Moreover, the manuscript highlights the contribution of the "chirurgia infusoria" as an innovative therapeutic system for an immediate and rapid recovery. From this perspective, blood transfusion represents a surgical practice for reanimation and resuscitation. The objective of this work was to analyze the importance of foreign literature and the English and French disputes presented by Davia in Italy, which made them known. Despite foreign prohibition in Italy, experiments with animal-to-human transfusions continued after 1648. A papal bull excommunicating scientists for conducting such research has never been found.

An unusual location of hand, foot and mouth disease.

Hand, foot, and mouth disease (HFMD) is a childhood febrile disease. Oral lesions and papulovesicular lesions on the hands and feet are the clinical signs of the disease. In our case, a 17-year-old boy presented to the emergency department, where he was diagnosed with HFMD. After 6 days, he felt intense pain in his right testicle, and therefore an ultrasound (US) examination was performed. US detected a hypoechoic mass-like area in the right testis. Viral etiology was suspected, and no therapy was prescribed. After a little more than 3 months, US examination showed a reduced lesion size. Viral epididymo-orchitis should be suspected in young men with a recent history of HFMD and testicular pain.

A silent laryngeal trauma case: an unexpected late fracture of the superior portion of the thyroid cartilage superior horn.

Attempts to analyze clinical unexpected cases of laryngeal fractures based on mild symptoms and physical findings. Even though a laryngeal fracture is rare in a living patient and when happens it is related to severe airways emergency, this case reported seems important to offer a possible differential diagnosis in patients who present with the same symptoms, if no other causes have been detected, like another one benign laryngeal disease.