Anatomical assessment of local recurrence site in breast cancer patients after breast reconstruction and post-mastectomy radiotherapy: implications for radiation volumes and techniques.

INTRODUCTION: Post-mastectomy radiotherapy (PMRT) improves local control rates and survival in patients with adverse prognostic features. The dose coverage to target volumes is critical to yield maximum benefit to treated patients, increasing local control and reducing risk of toxicity. This study aims to assess patterns of breast cancer relapse in patients treated with mastectomy, breast reconstruction and PMRT. METHODS: Breast cancer patients treated with PMRT between 1992 and 2017 were retrospectively reviewed. Clinical and pathological characteristics of patients were collected. Recurrences were defined as "in field," "marginal" or "out of field." Survival analyses were performed in relation to progression-free survival (PFS) and overall survival (OS). Correlation between baseline features was explored. RESULTS: Data of 140 patients are collected. After a median follow-up time of 72 months, median PFS and OS of 63 and 74 months were detected, respectively. Neoadjuvant chemotherapy, lympho-vascular space invasion (LVI) and size of primary tumor were all significantly associated with worst PFS and OS. Ten patients developed local recurrence: 30% "in field," 30% marginal recurrences, 20% "out of field" and 20% both "in field" and "out of field." No recurrence was detected under the expander, 80% above the device and 20% patients relapsed on IMN chain. The mean distant relapse-free survival was 39 months. Overall, 39 of 140 patients developed distant metastases. CONCLUSIONS: The onset of local-regional relapses occurred mainly above the expander/prosthesis, underlying the importance of inclusion of the subcutaneous tissues within the target volume. In order to refine new contouring recommendations for PMRT and breast reconstruction, future prospective studies are needed.

Impact of radiation dose on patient-reported acute taste alteration in a prospective observational study cohort in head and neck squamous cell cancer (HNSCC).

PURPOSE: Taste alteration (TA) is a frequent acute side effect of radiation treatment in HNSCC patients. Principal aim of our study was to investigate dosimetric parameters in relation to patient-assessed taste impairment in a prospective cohort treated with intensity-modulated radiotherapy. METHODS: All patients with locally advanced HNSCC and amenable to radical treatment were included. Chemotherapy-induced taste alteration scale (CITAS), EORTC QLQ-C30 and QLQ-HN43 questionnaires at baseline (T0), 3 weeks (T1) and 3 months (T2) after radiotherapy conclusion were used to assess taste impairment. Base of tongue, submandibular glands (SG), parotid glands (PG) and taste buds, along with anterior and medium third of the tongue, were considered as organs at risk and thus delineated according to consensus guidelines. The mean dose to the above-mentioned structures was correlated with patient-reported outcomes. RESULTS: Between September 2019 and November 2020, 33 patients were recruited, 31 of which analyzed. 71% had oropharyngeal carcinoma, mostly HPV-related (60%). All were treated with tomotherapy. 77.4% had concurrent cisplatin. Mean scores of general taste alterations, global health status and dry mouth and sticky saliva were assessed. The mean doses to the anterior third, medium third and base of the tongue were 23.85, 35.50 and 47.67 Gy, respectively. Taste buds received 32.72 Gy; right and left parotid 25 and 23 Gy; right and left submandibular glands 47.8 and 39.4 Gy. At univariate analysis, dysgeusia correlated with SG mean dose (95% CI 0-0.02 p = 0.05) and PG mean dose (95% CI 0-0.02 p = 0.05); dry mouth with mean dose to anterior (95% CI 0.03-1.47 p = 0.04) and medium third (95% CI 0.02-0.93 p = 0.04) of the tongue, to taste buds (95% CI 0.06-0.96 p = 0.03) and to SGs (95% CI 0.06-0.63 p = 0.02); pain mouth with mean dose to taste buds (95% CI 0-0.02 p = 0.04), to SGs (95% CI 0-0.03 p = 0.03) and to base tongue (95% CI 0-0.02 p = 0.02). CONCLUSIONS: Our analysis supports the influence of dose distribution on the development of TA in HNSCC patients. The contribution of dose to taste buds and tongue subvolumes remains unclear and worthy of further investigation.

Megaprostheses for the revision of infected hip arthroplasties with severe bone loss.

BACKGROUND: Periprosthetic hip infections with severe proximal femoral bone loss may require the use of limb salvage techniques, but no agreement exists in literature regarding the most effective treatment. Aim of this study is to analyze the infection eradication rate and implant survival at medium-term follow-up in patients treated with megaprostheses for periprosthetic hip infections with severe bone loss. METHODS: Twenty-one consecutive patients were retrospectively reviewed at a mean 64-month follow-up (24-120). Functional and pain scores, microbiological, radiological and intraoperative findings were registered. Kaplan Meier survival analysis and log rank test were used for infection free survival and implant survival analyses. RESULTS: The infection eradication rate was 90.5%, with an infection free survival of 95.2% at 2 years (95%CI 70.7-99.3) and 89.6%(95%CI 64.3-97.3) at 5 years. Only two patients required major implant revisions for aseptic implant loosening. The most frequent complication was dislocation (38.1%). The major revision-free survival of implants was 95.2% (95%CI 70.7-99.3) at 2 years and 89.6% (95%CI 64.3-97.3) at 5 years. The overall implant survival was 83.35% (CI95% 50.7-93.94) at 2 and 5 years. Subgroup analyses (cemented versus cementless MPs, coated versus uncoated MPs) revealed no significant differences at log rank test, but its reliability was limited by the small number of patients included. CONCLUSIONS: Proximal femoral arthroplasty is useful to treat periprosthetic hip infections with severe bone loss, providing good functional results with high infection eradication rates and rare major revisions at medium-term follow-up. No conclusions can be drawn on the role of cement and coatings.

Can the Leukocyte Esterase Strip Test Predict Persistence of Periprosthetic Joint Infection at Second-Stage Reimplantation?

BACKGROUND: We evaluated the reliability of intraoperative assessment of leukocyte esterase (LE) in synovial fluid samples from patients undergoing reimplantation following implant removal and spacer insertion for periprosthetic joint infection (PJI). Our hypothesis was that a positive intraoperative LE test would be a better predictor of persistent infection than either serum C-reactive protein (CRP) or erythrocyte sedimentation rate (ESR) or the combination of serum CRP and ESR. METHODS: The records of 76 patients who received a 2-stage exchange for PJI were retrospectively reviewed. Synovial fluid was collected for LE measurement during surgery before arthrotomy in 79 procedures. Receiver operating characteristic curves were generated. Sensitivity, specificity, positive predictive value, negative predictive value, accuracy, and area under the curve (AUC) of LE, CRP, ESR, and CRP + ESR were calculated. RESULTS: Sensitivity, specificity, positive predictive value, and negative predictive value of the LE assay were 82%, 99%, 90%, and 97%, respectively. Receiver operating characteristic analysis revealed an LE threshold of 1.5 between the first (negative) and the second (positive) level of the ordinal variable, so that a grade starting from 1+ was accurate for a diagnosis of persistent infection (AUC 0.9044). The best thresholds for the CRP and the ESR assay were 8.25 mg/L (82% sensitivity, 84% specificity, AUC 0.8416) and 45 mm/h (55% sensitivity, 87% specificity, AUC 0.7493), respectively. CONCLUSION: The LE strip test proved a reliable tool to diagnose persistence of infection and outperformed the serum CRP and ESR assays. The strip test provides a valuable intraoperative diagnostic during second-stage revision for PJI.

Is debridement really the best we can do for periprosthetic joint infections following total ankle replacements? A systematic review and meta-analysis.

BACKGROUND: Ankle periprosthetic joint infections are rising in number, but an evidence-based gold standard treatment has not been defined yet. METHODS: We made a systematic review about the operative treatment of infections following total ankle arthroplasty. Proportional meta-analysis was used to summarize effects of the surgical techniques included. Primary outcome of this study was infection eradication, followed by complications, re-interventions, amputation rates and functions. RESULTS: We included six studies(113 patients) reporting 6 types of surgical interventions, mostly irrigation and debridement (35.4%) and two-stage revisions (24.8%). No differences among all analyzed techniques were found in the infection eradication outcome as well as in the secondary outcomes. Patients receiving a permanent spacer are most likely to end up with amputation. CONCLUSIONS: Literature dealing with infections after total ankle replacement is currently composed by few low-quality articles. The overlapping of confidence intervals related to all analyzed interventions showed no superiority of either technique. LEVEL OF EVIDENCE: III.

Quadriceps muscle group function and after total knee arthroplasty-asystematic narrative update.

BACKGROUND: This article systematically summarizes the present evidences, published in the last 20 years, regarding the pre- and post-operative factors, which may influence recovery of the function of the quadriceps muscle group following total knee arthroplasty (TKA). We following the PRISMA methodology, including meta-analyses and high-level evidence studies (prospective trials, and, when unavailable, retrospective studies). SOURCES OF DATA: Pubmed and Cochrane databases: 582 articles were identified and 54 of them were selected. AREAS OF AGREEMENT: Tourniquets inflated at high pressure exert a detrimental effect on the quadriceps muscle group. Faster quadriceps recovery takes place using mini-invasive approaches, an eight-week rehabilitation period including balance training and the use of nutraceuticals. AREAS OF DISAGREEMENT: Pre-habilitation and pre-operative factors, analgesic methods and different TKA implants. GROWING POINTS AND AREAS TIMELY FOR DEVELOPING RESEARCH: Telerehabilitation seems a cost-effective tool for rehabilitation after TKA. Patients' optimization protocols before TKA should include standardized nutraceuticals intake.

What Is the Impact of a Previous Femoral Osteotomy on THA? A Systematic Review.

BACKGROUND: Femoral osteotomies have been widely used to treat a wide range of developmental and degenerative hip diseases. For this purpose, different types of proximal femur osteotomies were developed: at the neck as well as at the trochanteric, intertrochanteric, or subtrochanteric levels. Few studies have evaluated the impact of a previous femoral osteotomy on a THA; thus, whether and how a previous femoral osteotomy affects the outcome of THA remains controversial. QUESTIONS/PURPOSES: In this systematic review, we asked: (1) What are the most common complications after THA in patients who have undergone femoral osteotomy, and how frequently do those complications occur? (2) What is the survival of THA after previous femoral osteotomy? (3) Is the timing of hardware removal associated with THA complications and survivorship? METHODS: A systematic review was carried out on PubMed, the Cochrane Systematic Reviews Database, Scopus, and Embase databases with the following keywords: "THA", "total hip arthroplasty", and "total hip replacement" combined with at least one of "femoral osteotomy" or "intertrochanteric osteotomy" to achieve the maximum sensitivity of the search strategy. Identified studies were included if they met the following criteria: (1) reported data on THAs performed after femoral osteotomy; (2) recorded THA followup; (3) patients who underwent THA after femoral osteotomy constituted either the experimental group or a control group; (4) described the surgical and clinical complications and survivorship of the THA. The database search retrieved 383 studies, on which we performed a primary evaluation. After removing duplicates and completing a full-text evaluation for the inclusion criteria, 15 studies (seven historically controlled, eight case series) were included in the final review. Specific information was retrieved from each study included in the final analysis. The quality of each study was evaluated with the Methodological Index for Non-randomized Studies (MINORS) questionnaire. The mean MINORS score for the historically controlled studies was 14 of 24 (range, 10-17), whereas for the case series, it was 8.1 of 16 (range, 5-10). RESULTS: The proportion of patients who experienced intraoperative complications during THA ranged from 0% to 17%. The most common intraoperative complication was femoral fracture; other intraoperative complications were difficulties in hardware removal and nerve palsy; 15 studies reported on complications. The survivorship of THA after femoral osteotomy in the 13 studies that answered this question ranged from 43.7% to 100% in studies that had a range of followup from 2 to 20 years. The timing of hardware removal was described in five studies, three of which detailed more complications with hardware removal at the time of THA. CONCLUSIONS: This systematic review demonstrated that THA after femoral osteotomy is technically more demanding and may carry a higher risk of complications than one might expect after straightforward THA. Staged hardware removal may reduce the higher risk of intraoperative fracture and infection, but there is no clear evidence in support of this contention. Although survivorship of THA after femoral osteotomy was generally high, the studies that evaluated it were generally retrospective case series, with substantial biases, including selection bias and transfer bias (loss to followup), and so it is possible that survivorship of THA in the setting of prior femoral osteotomy may be lower than reported. LEVEL OF EVIDENCE: Level III, therapeutic study.

Cost-benefit analysis of antibiofilm microbiological techniques for peri-prosthetic joint infection diagnosis.

BACKGROUND: Implant-related infections, including those of peri-prosthetic joint (PJIs), osteosynthesis and other biomaterials, are biofilm-related. Pathogen identification is considered the diagnostic benchmark; however, the presence of bacterial biofilms makes pathogen detection with traditional microbiological techniques only partially effective. To improve microbiological diagnostic accuracy, some biofilm debonding techniques have been recently proposed. Aim of this health economics assessment study was to evaluate their economic impact on hospital costs. METHODS: Direct and indirect hospital costs connected with the routine introduction of sonication and dithiothreitol treatment applied to hip and knee PJIs and of tissue cultures were examined. In particular the consequences of diagnostic inaccuracy, the opportunities, costs, and risks of each technique were calculated. RESULTS: Considering an average of five samples per patient, processed separately with traditional tissue culture with or without sonication of prosthetic components, or pooled together using the MicroDTTect device (a close system for sample collection, transport and treatment with Dithiothreitol for microbial release from biofilm), the overall mean direct cost per patient was € 397 and € 393 for sonication or MicroDTTect, respectively, compared to € 308 for traditional tissue cultures. In terms of opportunity costs, MicroDTTect was the most effective technique, allowing for a 35% or 55% reduction in time required for sample treatment, compared to tissue cultures combined or not with sonication, respectively. Pooling together direct and indirect costs associated with false positive and negative results of the different diagnostic techniques, unnecessary medical treatments and possible medical claims, MicroDTTect or sonication become increasingly cost-effective when the extra-costs, generated by diagnostic inaccuracy of traditional tissue culture, took place, respectively, in 2% or 20% or more of the patients. CONCLUSIONS: This is the first study specifically focused on the economic impact of the routine clinical use of microbiological antibiofilm sampling and processing techniques in orthopaedics. Although our results may suffer from a potential country and hospital bias, as the data collection process for direct and indirect costs is specific to each institution and country, this analysis highlights the potential economic advantage to hospitals associated with the routine introduction of antibiofilm techniques for microbiological diagnosis of PJI.

Economic Evaluation of Antibacterial Coatings on Healthcare Costs in First Year Following Total Joint Arthroplasty.

BACKGROUND: Antibacterial coatings (ABCs) of implants have proven safe and effective to reduce postsurgical infection, but little is known about their possible economic impact on large-scale use. This study evaluated the point of economic balance, during the first year after surgery, and the potential overall annual healthcare cost savings of 3 different antibacterial technologies applied to joint arthroplasty: a dual-antibiotic-loaded bone cement (COPAL G + C), an antibacterial hydrogel coating (DAC), and a silver coating (Agluna). METHODS: The variables included in the algorithm were average cost and number of primary joint arthroplasties; average cost per patient of the ABC; incidence of periprosthetic joint infections and expected reduction using the ABCs; average cost of infection treatment and expected number of cases. RESULTS: The point of economic balance for COPAL G + C, DAC, and Agluna in the first year after surgery was reached in patient populations with an expected postsurgical infection rate of 1.5%, 2.6%, and 19.2%, respectively. If applied on a national scale, in a moderately high-risk population of patients with a 5% expected postsurgical infection rate, COPAL G + C and DAC hydrogel would provide annual direct cost savings of approximately €48,800,000 and €43,200,000 (€1220 and €1080 per patient), respectively, while the silver coating would be associated with an economic loss of approximately €136,000,000. CONCLUSION: This economic evaluation shows that ABC technologies have the potential to decrease healthcare costs primarily by decreasing the incidence of surgical site infections, provided that the technology is used in the appropriate risk class of patients.

The Concept of Biofilm-Related Implant Malfunction and "Low-Grade Infection".

Biofilms have a tremendous impact on industrial machines working in moist environments, while in biological systems their effect is further complicated by the host's response.Implant-related infections are a complex process, starting with bacterial adhesion and biofilm formation, followed by the variable interaction between host, implant, microorganisms and their by-products. Depending on the balance of these factors, different clinical presentations are observed, which may eventually, at times, shift from one into the other.-"Implant malfunction" displays only mild clinical signs/symptoms - light pain and/or slight soft tissue contracture or functional impairment - with negative infection/inflammatory markers; it requires prolonged cultures, antibiofilm and eventually genomic investigations for pathogen detection;-"Low-grade infection" features recurrent or persistent pain and/or soft tissue contracture with various functional impairment and mixed positive/negative markers of infection/inflammation; pathogen identification requires prolonged cultures and antibiofilm techniques;-"High-grade infection" displays classical signs/symptoms of infection/inflammation with positive tests; pathogen identification is often possible with traditional microbiological techniques, but is better achieved with prolonged cultures and antibiofilm processing.Understanding biofilms-related clinical presentations is crucial for physicians, to implement the best diagnostic and therapeutic measures, and for regulatory bodies, to define the evaluation process of technologies aimed at reducing implants' malfunctions and infections, like anti-adhesive and antibiofilm coatings, that should be regulated as (part of) medical devices, requiring a suitable post-marketing surveillance.Only an effective antibiofilm-targeted approach from all players will hopefully allow the medical community to mitigate the current unacceptable social and economical burden of implant-related infections and malfunctions.

The association of serum procalcitonin and high-sensitivity C-reactive protein with pneumonia in elderly multimorbid patients with respiratory symptoms: retrospective cohort study.

BACKGROUND: Serum procalcitonin and high-sensitivity C-reactive protein (hs-CRP) elevations have been associated with pneumonia in adults. Our aim was to establish their diagnostic usefulness in a cohort of hospitalized multimorbid patients ≥65 years old admitted to hospital with acute respiratory symptoms. METHODS: With a retrospective cohort study design, all multimorbid patients ≥65 years-old with acute respiratory symptoms admitted to an internal medicine hospital ward in Italy from January to August 2013 were evaluated. Pneumonia diagnosis, comorbidities expressed through Cumulative Illness Rating Scale (CIRS), setting of living, length of stay, serum hs-CRP and procalcitonin at admission were collected for each patient. Data were analyzed with Mann-Whitney's U test and multivariate Cox logistic regression analysis. A Receiver Operating Characteristic (ROC) curve was used to verify each biomarker's association with pneumonia diagnosis. RESULTS: Four hundred fifty five patients (227 M) were included in the study, of whom 239 with pneumonia (138 M, mean age 80 ± 13) and 216 without pneumonia (89 M, mean age 80 ± 14). After adjustment for age and sex, median levels of hs-CRP were significantly higher in patients with pneumonia (116 mg/L, IQR 46.5-179.0, vs 22.5 mg/dl, IQR 6.9-84.4, p < 0.0001), while procalcitonin median levels were not (0.22 ng/ml IQR 0.12-0.87, vs 0.15 ng/ml, IQR 0.10-0.35, p = 0.08). The ROC analysis showed that, unlike procalcitonin, hs-CRP values were predictive of pneumonia (AUC 0.76, 95% CI 0.72-0.79, p < 0.0001, cut-off value 61 mg/L), even after adjustment for possible confounders including nursing home residence and dementia. Serum hs-CRP levels >61 mg/L were independently associated with a 3.59-fold increased risk of pneumonia (OR 3.59, 95% CI 2.35-5.48, p < 0.0001). CONCLUSION: In elderly multimorbid patients who require hospital admission for respiratory symptoms, serum hs-CRP testing seems to be more useful than procalcitonin for guiding the diagnostic process when clinical suspicion of pneumonia is present. Procalcitonin testing might hence be not recommended in this setting.

Twenty-five years of idiopathic calcium nephrolithiasis: has anything changed?

Idiopathic calcium nephrolithiasis (ICN) is a disease whose prevalence is rising. Our aim was to assess whether lifestyle indicators and habits of calcium stone formers in Italy have changed over the last 25 years, trying to establish a connection with the diffusion of Internet access. Therefore we examined the database of the Stone Clinic of Parma University Hospital and extracted 1952 (1192 M, 760 F) patients with ICN who underwent a full clinical and laboratory evaluation from 1986 to 2010. Laboratory evaluation included data on urinary 24-h volume, pH, sodium, potassium, chloride, calcium, phosphate, uric acid, magnesium, oxalate, and citrate. Patients were split in three groups on a chronological basis, according to official EUROSTAT-ISTAT data of Internet connection among families in Italy: Group 1, pre-Internet era (1986-1998, 853 patients); Group 2, narrow-band era (1999-2004, 467 patients); Group 3, broad-band era (2005-2010, 632 patients). Over the time we found a significant increase in water intake (1.37 vs. 1.78 L in men and 1.21 vs. 1.55 L in women, Group 1 vs. Group 3, p-trend<0.001) and a decrease in urinary sodium and chloride for both genders and calcium and magnesium only for males, while females experienced a slight increase in oxalate excretion. Supersaturation indexes for calcium and uric acid stones dramatically fell for both genders. The percentage of stone formers performing physical activity significantly rise (41% Group 3 vs. 8% Group 1, p<0.001) and we also found a trend of reduction in mean blood pressure. Therefore, the lifestyle of Italian idiopathic calcium stone formers has changed over the last 25 years, and the rising Internet access may have played a great role in driving this change.

Cancer Treatment-Related Complications in Patients With Hypertrophic Cardiomyopathy.

OBJECTIVE: To describe the potential clinical cardiotoxicity of oncological treatments in a cohort of consecutive patients with hypertrophic cardiomyopathy (HCM), systematically followed-up at two national referral centers for HCM. Cardiotoxicity relates to the direct effects of cancer-related treatment on heart function, commonly presenting as left ventricular contractile dysfunction. However, limited data are available regarding cardiotoxic effects on HCM as most studies have not specifically analyzed the effects of oncological treatment in HCM populations. This gap in knowledge may lead to unjustified restriction of HCM patients from receiving curative cancer treatments. METHODS: We retrospectively analyzed clinical and instrumental data of all consecutive HCM patients who underwent oncological treatment between January 2000 and December 2020 collected in a centralized database. RESULTS: Of 3256 HCM patients, 121 (3.7%) had cancer; 110 (90.9%) underwent oncological surgery, 45 (37.2%) received chemotherapy, and 22 (18.2%) received chest radiation therapy (cRT). After a median follow-up of 5.2 years (Q1-Q3: 2-13 years) from oncological diagnosis, 32 patients died. The cumulative survival at 5 years was 79.9%. The cause of death was mainly attributed to the oncological condition, whereas four patients died of sudden cardiac death without receiving previous chemotherapy or cRT. No patient interrupted or reduced the dose of oncological treatment due to cardiac dysfunction. No sustained ventricular tachyarrhythmia was induced by chemotherapy or radiation therapy. CONCLUSION: Cancer treatment was well tolerated in HCM patients. In our consecutive series, none died of cardiovascular complications induced by chemotherapy or cRT and they did not require interruption or substantial treatment tapering due to cardiovascular toxic effects. Although a multidisciplinary evaluation is necessary and regimens must be tailored individually, the diagnosis of HCM per se should not be considered a contraindication to receive optimal curative cancer treatment.

Re-irradiation for recurrent intracranial meningiomas: Analysis of clinical outcomes and prognostic factors.

PURPOSE: Re-irradiation (re-RT) for recurrent intracranial meningiomas is hindered by the limited radiation tolerance of surrounding tissue and the risk of side effects. This study aimed at assessing outcomes, toxicities and prognostic factors in a cohort of patients with recurrent meningiomas re-treated with different RT modalities. MATERIALS AND METHODS: A multi-institutional database from 8 Italian centers including intracranial recurrent meningioma (RM) patients who underwent re-RT with different modalities (SRS, SRT, PT, EBRT) was collected. Biologically Equivalent Dose in 2 Gy-fractions (EQD2) and Biological Effective Dose (BED) for normal tissue and tumor were estimated for each RT course (α/ß = 2 for brain tissue and α/ß = 4 for meningioma). Primary outcome was second progression-free survival (s-PFS). Secondary outcomes were overall survival (OS) and treatment-related toxicity. Kaplan-Meier curves and Cox regression models were used for analysis. RESULTS: Between 2003 and 2021 181 patients (pts) were included. Median age at re-irradiation was 62 (range 20-89) and median Karnofsky Performance Status (KPS) was 90 (range 60-100). 78 pts were identified with WHO grade 1 disease, 65 pts had grade 2 disease and 10 pts had grade 3 disease. 28 pts who had no histologic sampling were grouped with grade 1 patients for further analysis. Seventy-five (41.4 %) patients received SRS, 63 (34.8 %) patients SRT, 31 (17.1 %) PT and 12 (6.7 %) EBRT. With a median follow-up of 4.6 years (interquartile range 1.7-6.8), 3-year s-PFS was 51.6 % and 3-year OS 72.5 %. At univariate analysis, SRT (HR 0.32, 95 % CI 0.19-0.55, p < 0.001), longer interval between the two courses of irradiation (HR 0.37, 95 % CI 0.21-0.67, p = 0.001), and higher tumor BED (HR 0.45 95 % CI 0.27-0.76, p = 0.003) were associated with longer s-PFS; in contrast, Ki67 > 5 % (HR 2.81, 95 % CI 1.48-5.34, p = 0.002) and WHO grade > 2 (HR 3.08, 95 % CI 1.80-5.28, p < 0.001) were negatively correlated with s-PFS. At multivariate analysis, SRT, time to re-RT and tumor BED maintained their statistically significant prognostic impact on s-PFS (HR 0.36, 95 % CI 0.21-0.64, p < 0.001; HR 0.38, 95 % CI 0.20-0.72, p = 0.003 and HR 0.31 95 % CI 0.13-0.76, p = 0.01, respectively). Acute and late adverse events (AEs) were reported in 38 (20.9 %) and 29 (16 %) patients. Larger tumor GTV (≥10 cc) was significantly associated with acute and late toxicity (p < 0.001 and p = 0.009, respectively). CONCLUSIONS: In patients with recurrent meningiomas, reirradiation is a feasible treatment option associated with acceptable toxicity profile. Prognostic factors in the decision-making process have been identified and should be incorporated in daily practice.

Three Months' PSA and Toxicity from a Prospective Trial Investigating STereotactic sAlvage Radiotherapy for Macroscopic Prostate Bed Recurrence after Prostatectomy-STARR (NCT05455736).

Biochemical recurrences after radical prostatectomy (RP) can be managed with curative purpose through salvage radiation therapy (SRT). RT dose escalation, such as stereotactic RT (SSRT), may improve relapse-free survival in this setting. STARR trial (NCT05455736) is a prospective multicenter study including patients affected by macroscopic recurrence within the prostate bed after RP treated with SSRT. Recurrence was detected with a Choline or PSMA CT-PET. In the current analysis, the early biochemical response (BR) rate and toxicity profile after three months of follow-up were assessed. Twenty-five patients were enrolled, and data about BR and toxicity at three months after treatment were available for 19 cases. Overall, BR was detected after three months in 58% of cases. Four G1-G2 adverse events were recorded; no G ≥ 3 adverse events were detected. SSRT appears feasible and safe, with more than half of patients experiencing BR and an encouraging toxicity profile. The STARR trial is one of the few prospective studies aimed at implementing this promising treatment strategy in this scenario.

Attitudes of Healthcare Workers toward Influenza Vaccination in the COVID-19 Era.

Healthcare workers (HCWs) are reluctant to participate in the influenza vaccination program, despite their high risk to contract and diffuse influenza due to professional exposure. The onset of the COVID-19 pandemic could raise HCW flu vaccination adherence. The aim of this study was to assess HCW attitudes toward influenza vaccination in the COVID-19 era. A multicenter observational study was carried out in three Italian hospitals (two in Pesaro and one in Fano, Marche region, Italy). Data about HCW influenza vaccination between 2013 and 2021 were extracted from the vaccination registers. An online questionnaire was sent to HCWs from July to October 2020 to assess their opinion about influenza vaccination in terms of knowledge, attitude, and practice during the COVID-19 pandemic. The number of flu-vaccinated HCWs increased from 3.7% in the 2013−2014 flu season to 53.6% in the 2020−2021 flu season (p < 0.001). About 15% (n = 324) of HCWs responded to the online questionnaire, and 30.5% of them declared that they had changed their minds on flu vaccination after the COVID-19 pandemic, deciding to get vaccinated. The COVID-19 pandemic significantly increased HCWs' attitudes toward flu vaccination. However, flu vaccination adherence remained low and should be improved.

Role of the prophylactic fixation of contralateral unaffected hip in paediatric unilateral slipped capital femoral epiphysis: a systematic review.

The aim of this systematic review is to assess the role of the prophylactic fixation of contralateral unaffected hip in unilateral slipped capital femoral epiphysis (SCFE) in children, focusing on the possible complications of this surgical procedure. A systematic review of medical literature was conducted, according to the Preferred Reporting Items for Systematic review and Meta-Analysis (PRISMA) statement, to analyse the complications of prophylactic contralateral hip fixation in unilateral paediatric SCFE. We registered the complications reported in the included studies, scoring their severity according to the orthopaedic adaptation of Clavien-Dindo classification. From 1695 studies primarily identified, 14 studies were finally included: 1 prospective cohort study, 4 retrospective case-control studies and 9 retrospective case series, with a total of 811 children diagnosed with unilateral SCFE and treated on the unaffected contralateral hip. Grade IV complications were very rare (0.37%), while the rate of grade III events was 8%. No death was recorded. The most frequent complication was unplanned further surgery (6.29%) that was an epiphyseal refixation, owing to the physiologic growth of the proximal femur, in 42 cases. Cannulated screws fixation showed to have a lower major complication rate than pinning with K-wires, 5.37% vs 17.95%. The prophylactic fixation of contralateral unaffected hip in paediatric unilateral SCFE is a safe procedure. Although a benefit-cost analysis on this topic has not been published yet, considering the low rate of complications, prophylactic hip fixation is a viable option for patients presenting with unilateral SCFE, to prevent the occurrence of severe hip deformity and avoid future invasive surgeries.

Integration between Novel Imaging Technologies and Modern Radiotherapy Techniques: How the Eye Drove the Chisel.

INTRODUCTION: Targeted dose-escalation and reduction of dose to adjacent organs at risk have been the main goal of radiotherapy in the last decade. Prostate cancer benefited the most from this process. In recent years, the development of Intensity Modulated Radiation Therapy (IMRT) and Stereotactic Body Radiotherapy (SBRT) radically changed clinical practice, also thanks to the availability of modern imaging techniques. The aim of this paper is to explore the relationship between diagnostic imaging and prostate cancer radiotherapy techniques. MATERIALS AND METHODS: Aiming to provide an overview of the integration between modern imaging and radiotherapy techniques, we performed a non-systematic search of papers exploring the predictive value of imaging before treatment, the role of radiomics in predicting treatment outcomes, implementation of novel imaging in RT planning and influence of imaging integration on use of RT in current clinical practice. Three independent authors (GF, IM and ID) performed an independent review focusing on these issues. Key references were derived from a PubMed query. Hand searching and clinicaltrials.gov were also used, and grey literature was searched for further papers of interest. The final choice of papers included was discussed between all co-authors. RESULTS: This paper contains a narrative report and a critical discussion of the role of new modern techniques in predicting outcomes before treatment, in radiotherapy planning and in the integration with systemic therapy in the management of prostate cancer. Also, the role of radiomics in a tailored treatment approach is explored. CONCLUSIONS: Integration between diagnostic imaging and radiotherapy is of great importance for the modern treatment of prostate cancer. Future clinical trials should be aimed at exploring the real clinical benefit of complex workflows in clinical practice.

Use of an alfa-lipoic, Methylsulfonylmethane, Boswellia serrata and Bromelain dietary supplement (OPERA®) for aromatase inhibitors-related arthralgia management (AIA): a prospective phase II trial (NCT04161833).

Aromatase Inhibitors (AIs) are recommended for the adjuvant treatment of hormone receptor positive breast cancer in both high-risk pre-menopausal and post-menopausal population; arthralgia is the main cause of discontinuation of therapy and affects up to 25% of population on AI treatment. The objective of the study was to prospectively evaluate OPERA® (GAMFARMA srl, Milan, Italy), a new dietary supplement where α-Lipoic acid, Boswellia serrata, Methylsulfonylmethane and Bromelain are combined in a single hard-gelatin capsule to be taken once a day. Fifty-three patients with arthralgia (NCI-CTCAE v4.0 grade ≥ 1) occurring during AI therapy were enrolled. All patients received OPERA® from enrollment (T0) up to sixth months (T3). Patients' AI-related arthralgia was evaluated every two months with VAS Scale, PRAI questionnaire, and CTCAE scale. Primary endpoint was the number of patients with symptom resolution (G0) at T3 if compared to T0, according to CTCAE and VAS scale. Secondary endpoints were decrease in arthralgia intensity measured with PRAI score at T3 compared to baseline, safety of OPERA® and rate of AI interruption. Treatment with OPERA® supplement was overall well tolerated; no relevant toxicities related to OPERA® intake were reported. Seven subjects (13.2%) were not included in the final analysis because of consent withdrawal. 46 participants were eligible for final analysis. According to CTCAE scale, 10 out of 46 patients reported symptoms resolution at 6-month follow-up from the time of enrollment T0 (p = 0.0009). According to VAS score, 5 patients reported complete resolution of symptoms at T3 if compared to baseline starting situation T0 (p = 0.0222). Analysis of PRAI score showed a significant reduction in arthralgia-related pain perceived (p = 0.0001). OPERA® was able to reduce the intensity of arthralgia related to AI therapy. Randomized, double-blind studies are warranted to confirm the effectiveness of this dietary supplement.

How SARS-CoV-2 Pandemic Changed Traumatology and Hospital Setting: An Analysis of 498 Fractured Patients.

BACKGROUND: SARS-CoV-2 pandemic is one of the biggest challenges for many health systems in the world, making lots of them overwhelmed by the enormous pressure to manage patients. We reported our Institutional Experience, with specific aims to describe the distribution and type of treated injuries, and the organizational setup of our hospital. METHODS: Data of fractured patients admitted for surgical treatment in the time frames 9 March 2020-4 May 2020 and 1 March 2019-31 May 2019 were collected and compared. Furthermore, surgery duration and some parameters of effectiveness in health management were compared. RESULTS: A total of 498 patients were included. Mean age significantly lower age in 2019 and femoral fractures were significantly more frequent 2020. Mean surgery time was significantly longer in 2020. Mortality rate difference between the two years was found to be statistically significant. Time interval between diagnosis and surgery and between diagnosis and discharge/decease was significantly lower in 2020. In 2020, no patient admitted with a negative swab turned positive in any of the following tests for SARS-CoV-2. CONCLUSIONS: The COVID-19 pandemic has modified the epidemiology of hospitalized patients for traumatic reasons, leading to an increased admission of older patients with femoral fractures. Nevertheless, our institutional experience showed that an efficient change in the hospital organization, with an improvement of several parameters of effectiveness in health management, led to a null infection rate between patients.