A methodological framework for rigorous systematic reviews: Tailoring comprehensive analyses to clinicians and healthcare professionals.

Systematic reviews represent a fundamental study design, providing the highest level of evidence across diverse research inquiries, encompassing both public health and clinical research and practice. However, for healthcare professionals, the process of selecting, synthesizing, and interpreting evidence can be challenging, and requires specialized skills. Therefore, it is imperative to explore innovative solutions aimed at simplifying and making the traditional systematic review process more accessible while ensuring the validity and reliability of results. In this perspective, our research objective is to develop a systematic review framework that, while maintaining a rigorous methodological approach, streamlines the process for healthcare professionals. This study describes such approach in every phase, from the collection of evidence to the writing of the text, creating a guide for the healthcare professional who approaches this type of research. The qualitative and organizational analysis tools are also described, providing useful information for the use of non-paid programs. This systematic review aims to develop a framework with a rigorous methodological approach that allows simplify the process for clinicians and healthcare professionals. The implementation of this methodology in clinical practice offers new perspectives to ensure a thoughtful consideration and application of scientific evidence and opens the way to innovative and easily accessible solutions to facilitate the conduct of systematic reviews in the clinical care setting.

A randomized prospective comparative study on sinonasal morbidity and quality of life of transsphenoidal endoscopic surgery for pituitary adenomas: endonasal versus trans-septal approach.

PURPOSE: Endoscopic endonasal transsphenoidal approach (Endonasal approach) is commonly used to treat pituitary adenomas. The extent of dissection possibly changes the anatomy and the physiology of the nasal cavities and could give rise to post-operative morbidity and the quality of life (QoL). The purpose of this study was to investigate sinonasal morbidity and general QoL in patients who underwent surgery for treatment of pituitary adenoma, comparing Endonasal and endoscopic trans-septal transsphenoidal approach (Trans-septal approach). METHODS: A prospective observational study, recruiting 40 patients undergoing surgery for pituitary adenoma, 20 via Endonasal approach and 20 via Trans-septal approach at our institution. Surveys with Sinonasal Outcome Test-22 (SNOT-22), Chronic Sinusitis Survey (CSS), and Short Form Health Survey 36 version 2 (SF-36v2) were obtained to collect QoL data pre- and postoperatively. RESULTS: All the 40 patients completed the questionnaires. At 6 months postoperatively, the SNOT-22 and CSS score shows significant improvements both in Endonasal approach (p = 0.01) and in Trans-septal approach (p = 0.02). No significant difference in sinonasal morbidity is observed between the two groups for SNOT-22 (p = 0.13) and CSS scores, except for sinus headache (p = 0.49), with a better score in Endonasal approach. The mean SF-36v2 scores remain the same in pre- and post-operative periods, but an improvement in time is seen in general health (p = 0.027), and general health compared to one year ago (p < 0.001). CONCLUSIONS: Endoscopic transsphenoidal surgery has negligible morbidity and does not negatively affect the nasal function in the long term. Endonasal approach and Trans-septal approach are comparable in terms of morbidity outcomes and general QoL, leaving the choice of the approach to the surgeon preference.

Ten-Year Follow-Up of Orbital Volume Augmentation With Calcium Hydroxyapatite Filler in Postenucleation Socket Syndrome.

PURPOSE: To describe the efficacy and persistence of injectable calcium hydroxyapatite (CAHY) to correct orbital volume deficit in postenucleation socket syndrome. METHODS: An observational study was conducted as a clinical review of all patients in the authors' practice who received injectable CAHY placed in the extraconal and intraconal space to increase orbital volume with a 10-year follow up. The amount of CAHY to be injected was defined according to the degree of orbital volume deficit. Patients previously treated with radiotherapy or with a conjunctival fornix insufficient to accommodate the external prosthesis were excluded. All the patients with at least 10 years of follow up were included in the study. RESULTS: Thirty-one postenucleation socket syndrome patients received injectable CAHY for orbital volume augmentation, with a 10-year follow up. The mean amount of preoperative relative enophthalmos measured by Hertel's exophthalmometry was 14.16 ± 2.15. An increase in the mean orbital volume of 3.35 ± 0.91 at 6 months and 2.97 ± 1.35 at 10 years was obtained. The mean follow-up was 219 ± 18 months (range, 184-240). Patients demonstrated clinical and cosmetic improvement that was observed to continue for 10 years. The complications were peribulbar ecchymosis, 2 extrusions of the internal prosthesis, and 2 ptosis. CONCLUSIONS: Injectable CAHY provides safe, simple, repeatable, and cost-effective technique to treat volume deficiency in the enophthalmic orbit in the long term. The volume augmentation obtained with this semipermanent filler demonstrated a lasting effect in the orbit with negligible loss of volume at 10 years.

Clinical and radiological outcomes of an uncemented metaphyseal short stem at minimum 10 years of follow-up: a prospective observational study.

PURPOSE: There is growing interest around short stems as they provide a less invasive approach for total hip arthroplasty preserving bone stock for a possible revision surgery if required. The main purpose of this work was to assess the long-term performance of an uncemented metaphyseal short stem in terms of survival rate and in addition its clinical and radiological outcomes. MATERIALS AND METHODS: From January to December 2010, we prospectively enrolled all consecutive patients undergoing primary total hip arthroplasty with an uncemented metaphyseal short stem in our institution with a minimum follow-up of 10 years. The radiographic features investigated were the varus-valgus stem orientation, areas of osteolysis and radiolucencies, stress shielding, and heterotopic calcifications. The clinical outcomes were measured using the HHS. RESULTS: A total of 163 patients (172 hips) were finally included and the measured survival rate at 10 years was 99.6%. The average HHS increased from 55.0 preoperatively to 97.8 at the last follow-up (p < 0.0001). Among them, 137 patients (164 hips) were also available for radiographic assessment. Mild varus malalignment was observed in 40% of cases and remained stable in the serial X-rays and was not associated with step loosening. Mild stress shielding was observed around 13 stems (9%) and moderate only around 3 implants. CONCLUSION: In conclusion, the uncemented metaphyseal short stems showed excellent survival and clinical results at 10 years and at a radiographical level very low stress shielding was observed; moreover, besides the high frequency of varus alignment the implanted stems was not associated with revision surgery or with worse clinical outcomes.

A new classification to characterize and predict treatment of acetabular bone defects.

BACKGROUND: The increasing amount of revision surgeries in total hip arthroplasty (THA) represents a burden for orthopedic surgeons given the complexity and unpredictability of this kind of surgery. The aim of the current study was to develop a new radiographic classification of acetabular bone defects stratify the severity of the lesion and to suggest the surgical strategy to address it. METHODS: Radiographs of 151 consecutive patients who underwent acetabular revision surgery in our institution were collected to develop a new classification that groups the acetabular bone defects in three zones (A, B and C). The performance to predict treatment and inter- and intra-rater agreement were evaluated. RESULTS: The ability of the newly proposed classification to predict treatment was 87.3% (k weighted: 0.65). The inter-rater reliability was 90.1% (k: 0.81), and the intra-rater reliability between the two sets of evaluations performed by the observer at 1-month distance was 97.5% (k: 0.94). CONCLUSIONS: The newly proposed classification was able to characterize the extent of acetabular bone defects and predict pre-operatively the appropriate surgical treatment strategy in 87.3% of cases. It showed a strong agreement among raters and an almost perfect agreement among different measurements at 1 month distance. This new tool could be used in the preoperative assessment to drive the use of secondary level image examinations and the type of surgical management.

Time-dependent effect of GLP-1 receptor agonists on cardiovascular benefits: a real-world study.

BACKGROUND: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have shown cardiovascular benefits in cardiovascular outcome trials in type 2 diabetes mellitus. However, the most convincing evidence was obtained in subjects with established cardiovascular (CV) disease. We analyzed the determinants of GLP-1 RA-mediated CV protection in a real-world population of persons with type 2 diabetes with and without a history of CV events with long-term follow-up. METHODS: Retrospective cohort study of 550 individuals with type 2 diabetes (395 in primary CV prevention, 155 in secondary CV prevention), followed at a single center after the first prescription of a GLP-1 RA between 2009 and 2019. CV and metabolic outcomes were assessed. RESULTS: Median duration of follow-up was 5.0 years (0.25-10.8) in primary prevention and 3.6 years (0-10.3) in secondary prevention, with a median duration of treatment of 3.2 years (0-10.8) and 2.5 years (0-10.3) respectively. In the multivariable Cox regression model considering GLP-1 RA treatment as a time-dependent covariate, in the primary prevention group, changes in BMI and glycated hemoglobin did not have an impact on MACE risk, while age at the time of GLP-1 initiation (HR 1.08, 95% CI 1.03-1.14, p = 0.001) and GLP-1 RA cessation by time (HR 3.40, 95% CI 1.82-6.32, p < 0.001) increased the risk of MACE. Regarding the secondary prevention group, only GLP-1 RA cessation by time (HR 2.71, 95% CI 1.46-5.01, p = 0.002) increased the risk of MACE. With respect to those who withdrew treatment, subjects who continued the GLP-1 RA had significantly greater weight loss and lower glycated hemoglobin levels during follow-up. CONCLUSIONS: In this real-world type 2 diabetes population, discontinuation of GLP-1 RA treatment was associated to a higher risk of major cardiovascular events, in both subjects with and without a history of CV events.

What Is the Appropriate Timing for Bar Removal After the Nuss Repair for Pectus Excavatum?

INTRODUCTION: The Nuss procedure for pectus excavatum requires that the sternal elevation be maintained by indwelling metal bars that are traditionally removed approximately 3 y after the repair. METHODS: A retrospective cohort study was conducted of all patients who underwent primary Nuss repair from 2007 to 2018 in two institutions and had a follow-up of at least 24 mo. Pectus bars had been left in place beyond 3 y in patients concerned over possible recurrence after bar removal. Structured interviews were held to assess pain, chest tightness, or other discomfort, and any adverse events related to pectus bars. Results were compared between patients in whom pectus bars were removed after 3 y (standard group) and those in whom bars were left in place longer (extended bar duration group). RESULTS: Two hundred and thirty-one patients (91% males, mean age 23.9 ± 8.3, mean Haller index 4.9 ± 2.3) were included. Bar duration was 30.6 ± 6.6 mo in the standard group (51 patients) versus 69.1 ± 26.3 mo in the extended group (180 patients). Some discomfort was reported by 81.6% in the standard group versus 62.9% in the extended group (P = 0.033), and discomfort occurring at least monthly or more often was only reported by 30% in the standard versus 30.3% in the extended group (P = 1.000). Quality of life improved in 92.6% of the standard group versus 94.7% of the extended group (P = 1.000). No significant adverse events were reported in either group. CONCLUSIONS: Our data suggest that an extended bar duration after the Nuss repair may not cause any adverse event nor negatively affect quality of life.

Reliability of pulse pressure and stroke volume variation in assessing fluid responsiveness in the operating room: a metanalysis and a metaregression.

BACKGROUND: Pulse pressure and stroke volume variation (PPV and SVV) have been widely used in surgical patients as predictors of fluid challenge (FC) response. Several factors may affect the reliability of these indices in predicting fluid responsiveness, such as the position of the patient, the use of laparoscopy and the opening of the abdomen or the chest, combined FC characteristics, the tidal volume (Vt) and the type of anesthesia. METHODS: Systematic review and metanalysis of PPV and SVV use in surgical adult patients. The QUADAS-2 scale was used to assess the risk of bias of included studies. We adopted a metanalysis pooling of aggregate data from 5 subgroups of studies with random effects models using the common-effect inverse variance model. The area under the curve (AUC) of pooled receiving operating characteristics (ROC) curves was reported. A metaregression was performed using FC type, volume, and rate as independent variables. RESULTS: We selected 59 studies enrolling 2,947 patients, with a median of fluid responders of 55% (46-63). The pooled AUC for the PPV was 0.77 (0.73-0.80), with a mean threshold of 10.8 (10.6-11.0). The pooled AUC for the SVV was 0.76 (0.72-0.80), with a mean threshold of 12.1 (11.6-12.7); 19 studies (32.2%) reported the grey zone of PPV or SVV, with a median of 56% (40-62) and 57% (46-83) of patients included, respectively. In the different subgroups, the AUC and the best thresholds ranged from 0.69 and 0.81 and from 6.9 to 11.5% for the PPV, and from 0.73 to 0.79 and 9.9 to 10.8% for the SVV. A high Vt and the choice of colloids positively impacted on PPV performance, especially among patients with closed chest and abdomen, or in prone position. CONCLUSION: The overall performance of PPV and SVV in operating room in predicting fluid responsiveness is moderate, ranging close to an AUC of 0.80 only some subgroups of surgical patients. The grey zone of these dynamic indices is wide and should be carefully considered during the assessment of fluid responsiveness. A high Vt and the choice of colloids for the FC are factors potentially influencing PPV reliability. TRIAL REGISTRATION: PROSPERO (CRD42022379120), December 2022. https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=379120.

Diagnostic Performance and Clinical Impact of PSMA PET/CT versus mpMRI in Patients with a High Suspicion of Prostate Cancer and Previously Negative Biopsy: A Prospective Trial (PROSPET-BX).

BACKGROUND: This prospective single-arm study is designed to compare in parallel 68Ga-PSMA PET/TRUS (transrectal or transperineal) fusion biopsy ("experimental test") with multiparametric MRI (mpMRI)/TRUS fusion prostate biopsy ("standard test") in men with a high suspicion of prostate cancer (PCa) after at least one negative biopsy. The primary objective was to evaluate the diagnostic performance of 68Ga-PSMA PET/TRUS fusion prostate biopsy in comparison to mpMRI/TRUS fusion prostate biopsy analyzed in parallel. Secondarily, we aimed to determine the relationship between the "experimental test" and the histopathological characteristics of the specimen, along with the clinical utility of the "experimental test" compared to the "standard test." SUMMARY: To test the superiority of 68Ga-PSMA PET/CT compared to mpMRI, we will enroll a minimum cohort of 128 patients. Inclusion criteria comprise: age >18 years; blood PSA level >4.0 ng/mL; free-to-total PSA ratio <20%; progressive rise of PSA levels in two consecutive blood samples despite antibiotics; serum blood tests suspicious for PCa; at least one previous negative biopsy; ASAP and/or high-grade PIN; negative digital rectal examination. All eligible patients will undergo 68Ga-PSMA PET/CT and mpMRI scans within 1 month's distance from each other, followed by biopsy session to be completed within 1 month's distance. Targeted TRUS fusion needle biopsy will be performed for all lesions detected with PET and mpMRI. The total duration of the study is 36 months. KEY MESSAGES: By comparing the "experimental test" and the "standard test" in parallel, we will be able to determine the superior diagnostic performance of 68Ga-PSMA PET/CT over mpMRI in detecting PCa, and in particular clinically significant PCa, in the specific cohort of patients with a high suspicion of PCa who are candidates to re-biopsy. The clinical impact of the "experimental test" will be subsequently analyzed in terms of the number of prostate biopsies that could be spared, time-consuming, patient friendliness, and cost-effectiveness.

Increased Time to Surgery After Anterior Cruciate Ligament Tear in Female Patients Results in Greater Risk of Medial Meniscus Tear: A Study of 489 Female Patients.

PURPOSE: This study assessed the incidence of meniscal tears in anterior cruciate ligament (ACL)-deficient knees, considering the time between injury and reconstruction in a large sample of female patients. Furthermore, we evaluated whether the rate of meniscal repair or meniscectomy was affected by age and body mass index (BMI). METHODS: The medical records of 489 patients who underwent ACL-reconstructive surgery between January 2011 and April 2021 were analyzed to collect data on the prevalence of meniscal tears, surgical timing, patient age, and BMI. Logistic regression was performed to estimate the association between the prevalence of meniscal tears and the independent variables of surgical timing, age, and BMI. RESULTS: Between 24 and 60 months after their injury, female patients showed a statistically significant increase in the presence of associated meniscal lesions when compared with ACL reconstruction performed earlier (odds ratio [OR] of 3.11; 95% 1.06-9.10 confidence interval [CI]), especially for medial meniscal tears, with an OR of 1.94 (95% CI 1.23-3.05, P = .004) between 12 and 24 months. There is a statistically significant difference after 12 months in the rate of meniscal suturing for medial meniscus tears (OR 3.30; CI 1.37-7.91 P = .007). Increasing age was associated with a greater prevalence of meniscal tears up to 30-50 years, but there was no clear association between BMI and associated lesions other than a greater rate of meniscectomies. CONCLUSIONS: In female patients who experienced an ACL injury, a delay in surgery greater than 12 months is associated with a gradual increase in the risk of nonrepairable medial meniscal tear; this risk becomes statistically significant after 24 months. A high BMI does not seem to have relevance in the onset of associated lesions in women but results in a greater rate of meniscectomies compared with meniscal sutures, whereas age between 30 and 50 years is associated with a greater risk of associated injuries. LEVEL OF EVIDENCE: III, retrospective comparative prognostic trial.

Steps forward in embryo transfer technique: a retrospective study comparing direct versus afterload catheters at different time frames.

PURPOSE: To assess whether embryo transfer (ET) technique can influence the clinical pregnancy rate (CPR) and its correlation with the embryo transfer difficulty. DESIGN: This single center retrospective cohort analysis of fresh and frozen single blastocyst transfers performed between January 2016 and December 2021 included fresh and frozen single blastocyst transfers performed during the study timeframe. Direct technique was the only one used from January 2016 to September 2017. From September 2017 to March 2019, the choice between the two techniques was given by randomization, due to a clinical trial recruitment. From April 2019, only the afterload technique was used. Preimplantation genetic testing cycles and gamete donation procedures and cycles performed with external gametes or embryos were excluded. CPR was the primary outcome, while difficult transfer rate the secondary one. Univariate and multivariate logistic regressions were performed. RESULTS: During the period, 8,189 transfers were performed. CPR of the afterload group resulted significantly higher compared to the direct group (44.69% versus 41.65%, OR 1.13, 95% CI 1.02-1.25, p = 0.017) and the rate of difficult transfers two-thirds lower (9.06% versus 26.85%, OR 0.27, 95% CI 0.24-0.31, p < 0.001). CONCLUSION: Our study demonstrated that CPR is significantly affected by the ET technique. In particular, with the afterload protocol, both CPR and easy transfer rates increased. TRIAL REGISTRATION: http://clinicaltrials.gov registration number: NCT05364528, retrospectively registered on 3rd of May 2022.

A BMI above 30 results in satisfying outcomes in patients undergoing fixed-bearing lateral unicompartmental knee arthroplasty.

PURPOSE: The purpose of this study is to analyse the effect of BMI on clinical outcomes of cemented fixed-bearing lateral unicompartmental knee arthroplasty (UKA) on a 2- to 12-year follow-up. METHODS: Between January 2010 and January 2020, a total of 103 lateral UKAs were implanted. The Oxford Knee Score (OKS) and the Western Ontario and McMaster University Osteoarthritis Index for pain, stiffness, function, and total score were administered to estimate patients' overall health status pre- and post-operatively. Results were considered good or excellent for WOMAC values > 85 points and OKS > 40 points. Survivorship, described with Kaplan-Meier method, was defined as the lack of revision at the latest follow-up. Complications or further operations were recorded. p values of < 0.05 were considered significant. RESULTS: One hundred one lateral UKAs were assessed at a mean follow-up of 77.8 months. No patients underwent revision, but 2 patients (2, 0%) developed aseptic loosening of the implant 2 and 5 years after surgery but for clinical reasons neither undergo revision (5-year survivor 97.2%). Overall satisfaction was generally high, with excellent scores in all WOMAC subscales and OKS for all BMI groups. Considering the pain subscale (WOMAC pain), patients with normal weight and overweight achieve excellent results more frequently [10 (25.64%) vs 10 (23.81%) p = 0.026] than obese patients (n = 0); on the other hand, considering the quality of life (WOMAC QoL), obese patients most frequently reach excellent values, even statistically significant [n = 15 (75.00%) p = 0.040]. CONCLUSION: Although obesity has historically been described as a contraindication to UKA, improved outcomes with modern UKA implant designs have challenged this perception. Therefore, the classic contraindication of UKAs in patients with BMI > 30 kg/m2 may not be justified. According to the present study, lateral UKA patients with BMI > 30 kg/m2 had satisfactory patient-reported outcome measures compared to non-obese patients on a long term with survival rates comparable to medial UKA. Obese patients should not be excluded from the benefit of lateral UKA surgery.

Early application of extracorporeal shock wave therapy improves pain control and functional scores in patients undergoing total knee arthroplasty: a randomized controlled trial.

PURPOSE: The use of biophysical stimuli produced by extracorporeal shock wave therapy (ESWT) can improve the rehabilitation treatment of patients undergoing total knee arthroplasty (TKA). The aim of our study is to evaluate the short-term efficacy of early postoperative ESWT in combination with physiotherapy in terms of pain reduction and motor function recovery of patients undergoing TKA and compare it with conventional physiotherapy treatment. METHODS: Fifty-six patients undergoing TKA were enrolled in the study from January 2019 to February 2020. Patients received two sessions of physiotherapy daily, with (experimental group) or without (control group) four sessions of ESWT within seven days after surgery. Patients were prospectively evaluated at baseline and at post-operative day two and seven. Assessment included active knee range of motion (aROM), timed up and go (TUG) test, visual analogue scale (VAS) for pain, and Borg scale. RESULTS: Fifty patients completed the study. Both treatments proved to be effective in reducing pain and improving the knee range of motion and functional scores at seven days after surgery: the aROM in the ESWT group was 36.8 ± 11.0 grades (p < 0.001), while in control group was 19.8 ± 7.8 grades (p < 0.001). TUG, VAS, and BORG scores showed a similar trend. Comparative analysis revealed superior clinical results for the experimental group in all the outcomes, in particular aROM (96.0 ± 5.40 vs. 81.20 ± 11.01, p < 0.001) and TUG test (17.4 ± 5.61 vs. 21.24 ± 5.88, p < 0.001), at day seven after surgery. CONCLUSION: Early application of ESWT in addition to physiotherapy can positively influence the rehabilitation process after TKA. The treatment proved to be well tolerated and safe. Preliminary results demonstrated better pain control and functional scores compared to physiotherapy alone.

Modulation of NBAS-Related Functions in the Early Response to SARS-CoV-2 Infection.

Upon infection, severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) is predicted to interact with diverse cellular functions, such as the nonsense-mediated decay (NMD) pathway, as suggested by the identification of the core NMD factor upframeshift-1 (UPF1) in the SARS-CoV-2 interactome, and the retrograde transport from the Golgi to the endoplasmic reticulum (ER) through the endoplasmic reticulum-Golgi intermediate compartment (ERGIC), where coronavirus assembly occurs. Here, we investigated the expression and localization of the neuroblastoma-amplified sequence (NBAS) protein, a UPF1 partner for the NMD at the ER, participating also in retrograde transport, and of its functional partners, at early time points after SARS-CoV-2 infection of the human lung epithelial cell line Calu3. We found a significant decrease of DExH-Box Helicase 34 (DHX34), suppressor with morphogenetic effect on genitalia 5 (SMG5), and SMG7 expression at 6 h post-infection, followed by a significant increase of these genes and also UPF1 and UPF2 at 9 h post-infection. Conversely, NBAS and other genes coding for NMD factors were not modulated. Known NMD substrates related to cell stress (Growth Arrest Specific 5, GAS5; transducin beta-like 2, TBL2; and DNA damage-inducible transcript 3, DDIT3) were increased in infected cells, possibly as a result of alterations in the NMD pathway and of a direct effect of the infection. We also found that the expression of unconventional SNARE in the ER 1, USE1 (p31) and Zeste White 10 homolog, ZW10, partners of NBAS in the retrograde transport function, significantly increased over time in infected cells. Co-localization of NBAS and UPF1 proteins did not change within 24 h of infection nor did it differ in infected versus non-infected cells at 1 and 24 h after infection; similarly, the co-localization of NBAS and p31 proteins was not altered by infection in this short time frame. Finally, both NBAS and UPF1 were found to co-localize with SARS-CoV-2 S and N proteins. Overall, these data are preliminary evidence of an interaction between NBAS and NBAS-related functions and SARS-CoV-2 in infected cells, deserving further investigation.

Safety of autologous fat grafting in breast cancer: a multicenter Italian study among 17 senonetwork breast units autologous fat grafting safety: a multicenter Italian retrospective study.

BACKGROUND: Autologous fat grafting (AFG), defined as the re-implant to the breast of fat tissue from different body areas, has been firstly applied to esthetic plastic surgery and then has moved to reconstructive surgery, mainly used for scar correction and opposite breast altering. Nevertheless, due to the potentially unsafe stem-like properties of adipocytes at the tumoral bed level, no clear evidence of the procedure's oncological safety has been clearly documented at present. PATIENTS AND METHODS: We retrospectively collected data of early breast cancer (BC) patients from 17 Italian Breast Units and assessed differences in terms of locoregional recurrence rate (LRR) and locoregional recurrence-free survival (LRFS) between patients who underwent AFG and patients who did not. Differences were analyzed in the entire cohort of invasive tumors and in different subgroups, according to prognostic biological subtypes. RESULTS: With a median follow-up time of 60 months, LRR was 5.3% (n = 71) in the matched population, 3.9% (n = 18) in the AFG group, and 6.1% (n = 53) in the non-AFG group, suggesting non-inferiority of AFG (p = 0.084). Building Kaplan-Meier curves confirmed non-inferiority of the AFG procedure for LRFS (aHR 0.73, 95% CI 0.41-1.30, p = 0.291). The same effect, in terms of LRFS, was also documented among different biological subtypes (luminal-like group, aHR 0.76, 95% CI 0.34-1.68, p = 0.493; HER2 enriched-like, aHR 0.89, 95% CI 0.19-4.22, p = 0.882; and TNBC, aHR 0.61, 95% CI 0.12-2.98, p = 0.543). CONCLUSIONS: Our study confirms in a very large, multicenter cohort of early BC patients that, aside the well-known benefits on the esthetic result, AFG do not interfere negatively with cancer prognosis.

Different actors for the same play: the impact of the embryologist performing the embryo transfer.

RESEARCH QUESTION: Does the embryologist performing the embryo transfer impact the cycle outcome, in terms of ongoing pregnancy rate (OPR)? DESIGN: This single-centre retrospective study analysed the results, corrected for main confounders, from 28 embryologists and 32 physicians who performed respectively 24,992 and 24,669 fresh embryo transfers (either at cleavage or blastocyst stage) during a 20-year period from January 2000 to December 2019, in a university-affiliated tertiary care assisted reproductive technology (ART) centre. Primary outcome was OPR, defined as the number of viable pregnancies that had completed at least 12 weeks of gestation on the total number of embryo transfers performed. The study also assessed whether the embryologist's experience, measured in terms of number of embryo transfers performed prior to the day of the procedure, had an impact on their performance. The secondary aim was to assess which variable, between the embryologist and physician, more significantly impacted OPR. RESULTS: The overall unadjusted OPR was 22.54%. The embryologist performing the embryo transfer was found to significantly affect the OPR (P < 0.0001), corrected for potential confounders. However, the physician factor made a slightly greater contribution to the model (likelihood ratio 21.86, P < 0.001 versus likelihood ratio 17.20, P < 0.0001). No significant association was found between the experience of the embryologist and OPR (P = 0.067). CONCLUSIONS: These results show how the 'human factor' influences the chances of a positive outcome in the final step of a high-tech procedure and underline the importance of implementing an operator quality performance programme (both for physicians and embryologists) to ensure the maintenance of benchmark results and eventually retrain underperforming operators.

Fluid challenge in critically ill patients receiving haemodynamic monitoring: a systematic review and comparison of two decades.

INTRODUCTION: Fluid challenges are widely adopted in critically ill patients to reverse haemodynamic instability. We reviewed the literature to appraise fluid challenge characteristics in intensive care unit (ICU) patients receiving haemodynamic monitoring and considered two decades: 2000-2010 and 2011-2021. METHODS: We assessed research studies and collected data regarding study setting, patient population, fluid challenge characteristics, and monitoring. MEDLINE, Embase, and Cochrane search engines were used. A fluid challenge was defined as an infusion of a definite quantity of fluid (expressed as a volume in mL or ml/kg) in a fixed time (expressed in minutes), whose outcome was defined as a change in predefined haemodynamic variables above a predetermined threshold. RESULTS: We included 124 studies, 32 (25.8%) published in 2000-2010 and 92 (74.2%) in 2011-2021, overall enrolling 6,086 patients, who presented sepsis/septic shock in 50.6% of cases. The fluid challenge usually consisted of 500 mL (76.6%) of crystalloids (56.6%) infused with a rate of 25 mL/min. Fluid responsiveness was usually defined by a cardiac output/index (CO/CI) increase ≥ 15% (70.9%). The infusion time was quicker (15 min vs 30 min), and crystalloids were more frequent in the 2011-2021 compared to the 2000-2010 period. CONCLUSIONS: In the literature, fluid challenges are usually performed by infusing 500 mL of crystalloids bolus in less than 20 min. A positive fluid challenge response, reported in 52% of ICU patients, is generally defined by a CO/CI increase ≥ 15%. Compared to the 2000-2010 decade, in 2011-2021 the infusion time of the fluid challenge was shorter, and crystalloids were more frequently used.

Retrospective comparison of pregnancy outcomes of fresh and frozen-warmed single blastocyst transfer: a 5-year single-center experience.

PURPOSE: To assess whether live birth rates (LBR) and maternal/neonatal complications differed following single fresh and frozen-warmed blastocyst transfer. METHODS: The present retrospective observational study analyzed 4,613 single embryo transfers (SET) (646 fresh and 3,967 frozen) from January 1, 2014, to December 31, 2018. Fresh embryo transfer at blastocyst stage was considered according to the age of the patient and her prognosis. In case of the risk of ovarian hyperstimulation syndrome, premature progesterone rise, non-optimal endometrial growth, or supernumerary embryos, cryopreservation with subsequent frozen embryo transfer (FET) was indicated. RESULTS: No differences in LBR were recorded. Fresh embryo transfers yielded an increase both in neonatal complications OR 2.15 (95% CI 1.20-3.86, p 0.010), with a higher prevalence of singletons weighting below the 5th percentile (p 0.013) and of intrauterine growth retardation (p 0.015), as well as maternal complications, with a higher placenta previa occurrence OR 3.58 (95% CI 1.54-8.28, p 0.003), compared to FET. CONCLUSION: LBR appears not to be affected by the transfer procedure preferred. Fresh embryo transfer is associated with higher risk of neonatal complications (specifically a higher prevalence of singletons weighting below the 5th percentile and of intrauterine growth retardation) and placenta previa. Reflecting on the increased practice of ART procedures, it is imperative to understand whether a transfer procedure yields less complications than the other and if it is time to switch to a "freeze-all" procedure as standard practice. TRIAL REGISTRATION: Clinical Trial Registration Number: NCT04310761. Date of registration: March 17, 2020, retrospectively registered.

Association between human papillomavirus infection and malignant transformation of sinonasal inverted papilloma: A systematic review and meta-analysis.

PURPOSE: Although sinonasal inverted papilloma malignant transformation has not been entirely understood, some studies have suggested that human papillomavirus acts as a potential oncogenic agent in the progression of sinonasal inverted papilloma to squamous cell carcinoma. The purpose of this study was to assess the association between human papillomavirus infection and sinonasal inverted papilloma transformation, taking also into account human papillomavirus types and their distribution in different geographic areas. MATERIALS AND METHODS: The literature from the last 25 years was examined. The systematic review and meta-analysis were performed according to the PRISMA guidelines. RESULTS: A total of 163 malignant sinonasal inverted papilloma and 961 non-malignant sinonasal inverted papilloma were included in the overall analysis. From this sample it was possible to recognize a statistically significant increase in risk of malignancy of sinonasal inverted papilloma for human papillomavirus infection (OR = 2.43, 95 % CI: 1.45-4.08, I2 = 14.0 %). A positive association for patients with high-risk human papillomavirus types was noted (OR = 10.20, 95 % CI: 3.66-28.42, I2 = 15.9 %). In all the 3 geographical areas analyzed the presence of high-risk human papillomavirus significantly increased the probability of malignant transformation. CONCLUSIONS: High-risk human papillomavirus infection plays a key role in the malignant transformation of sinonasal inverted papilloma and its research during histological examination can be of paramount importance. More prospective studies are needed to help further tease out this association.

Dipeptidyl Peptidase 3 Activity as a Promising Biomarker of Bone Fragility in Postmenopausal Women.

The dipeptidyl peptidase 3 (Dpp3) is a ubiquitous zinc-dependent aminopeptidase, participating in the activation or degradation of signaling peptides and in the Keap1−Nrf2 antioxidant pathway. The absence of Dpp3 in the Dpp3 knockout mouse model causes increased osteoclast activity, altered osteogenic function, sustained oxidative stress in the bone tissue, and bone loss. We aimed to assess the association of Dpp3 activity with bone fragility in postmenopausal osteoporosis and the impact of denosumab on enzymatic activity. We conducted a two-phase study including 69 postmenopausal women with severe osteoporosis and 36 postmenopausal women without osteometabolic conditions, as controls (cross-sectional phase). Subjects with severe osteoporosis were assessed at baseline and 14 days after the first denosumab administration (prospective phase). The results showed significant reduction in serum Dpp3 activity (expressed as nmoles of formed product/mg proteins/min) in patients vs. controls (0.791 ± 0.232 vs. 1.195 ± 0.338; p < 0.001), and significant association with bone mass at the femoral neck (r = 0.28, p = 0.02) in patients prior to treatment. We found a negative correlation between C-terminal telopeptide (CTX) or N-terminal pro-peptide of type 1 procollagen (P1NP) levels and Dpp3 activity (respectively, r = −0.29, p = 0.012; and r = −0.2572, p = 0.033). Dpp3 activity did not change after denosumab injection. Our findings support a critical role played by Dpp3 in bone homeostasis as a potential bone protective factor. Additional clinical studies in larger cohorts might explore the implementation of Dpp3 assessment as a biomarker of bone health status.