The impact of mpMRI-targeted vs systematic biopsy on the risk of prostate cancer downgrading at final pathology.

PURPOSE: Although targeted biopsies (TBx) are associated with improved disease assessment, concerns have been raised regarding the risk of prostate cancer (PCa) overgrading due to more accurate biopsy core deployment in the index lesion. METHODS: We identified 1672 patients treated with radical prostatectomy (RP) with a positive mpMRI and ISUP ≥ 2 PCa detected via systematic biopsy (SBx) plus TBx. We compared downgrading rates at RP (ISUP 4-5, 3, and 2 at biopsy, to a lower ISUP) for PCa detected via SBx only (group 1), via TBx only (group 2), and eventually for PCa detected with the same ISUP 2-5 at both SBx and TBx (group 3), using multivariable logistic regression models (MVA). RESULTS: Overall, 12 vs 14 vs 6% (n = 176 vs 227 vs 96) downgrading rates were recorded in group 1 vs group 2 vs group 3, respectively (p < 0.001). At MVA, group 2 was more likely to be downgraded (OR 1.26, p = 0.04), as compared to group 1. Conversely, group 3 was less likely to be downgraded at RP (OR 0.42, p < 0.001). CONCLUSIONS: Downgrading rates are highest when PCa is present in TBx only and, especially when the highest grade PCa is diagnosed by TBx cores only. Conversely, downgrading rates are lowest when PCa is identified with the same ISUP through both SBx and TBx. The presence of clinically significant disease at SBx + TBx may indicate a more reliable assessment of the disease at the time of biopsy potentially reducing the risk of downgrading at final pathology.

Prediction of large-for-gestational age at 36 weeks' gestation: two-dimensional ultrasound vs three-dimensional ultrasound vs magnetic resonance imaging.

OBJECTIVE: To compare the performance of two-dimensional ultrasound (2D-US), three-dimensional ultrasound (3D-US) and magnetic resonance imaging (MRI) at 36 weeks' gestation in predicting the delivery of a large-for-gestational-age (LGA) neonate, defined as birth weight ≥ 95th percentile, in patients at high and low risk for macrosomia. METHODS: This was a secondary analysis of a prospective observational study conducted between January 2017 and February 2019. Women with a singleton pregnancy at 36 weeks' gestation underwent 2D-US, 3D-US and MRI within 15 min for estimation of fetal weight. Weight estimations and birth weight were plotted on a growth curve to obtain percentiles for comparison. Participants were considered high risk if they had at least one of the following risk factors: diabetes mellitus, estimated fetal weight ≥ 90th percentile at the routine third-trimester ultrasound examination, obesity (prepregnancy body mass index ≥ 30 kg/m2) or excessive weight gain during pregnancy. The outcome was the diagnostic performance of each modality in the prediction of birth weight ≥ 95th percentile, expressed as the area under the receiver-operating-characteristics curve (AUC), sensitivity, specificity and positive and negative predictive values. RESULTS: A total of 965 women were included, of whom 533 (55.23%) were high risk and 432 (44.77%) were low risk. In the low-risk group, the AUCs for birth weight ≥ 95th percentile were 0.982 for MRI, 0.964 for 2D-US and 0.962 for 3D-US; pairwise comparisons were non-significant. In the high-risk group, the AUCs were 0.959 for MRI, 0.909 for 2D-US and 0.894 for 3D-US. A statistically significant difference was noted between MRI and both 2D-US (P = 0.002) and 3D-US (P = 0.002), but not between 2D-US and 3D-US (P = 0.503). In the high-risk group, MRI had the highest sensitivity (65.79%) compared with 2D-US (36.84%, P = 0.002) and 3D-US (21.05%, P < 0.001), whereas 3D-US had the highest specificity (98.99%) compared with 2D-US (96.77%, P = 0.005) and MRI (96.97%, P = 0.004). CONCLUSIONS: At 36 weeks' gestation, MRI has better performance compared with 2D-US and 3D-US in predicting birth weight ≥ 95th percentile in patients at high risk for macrosomia, whereas the performance of 2D-US and 3D-US is comparable. For low-risk patients, the three modalities perform similarly. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

Changes in serum PSA after endoscopic enucleation of the prostate are predictive for the future diagnosis of prostate cancer.

PURPOSE: After Endoscopic Enucleation of the Prostate (EEP) for benign prostatic obstruction (BPO), men remain at risk for prostate cancer (PCa). Significant PSA changes occur after enucleation, which interfere with later screening for PCa. It remains unclear which patients need further diagnostic investigations for PCa after EEP. The goal of this study was to identify an independent predictor for PCa diagnosis after Holmium Laser Enucleation of the Prostate (HoLEP) in patients whose HoLEP resection specimen did not show PCa. METHODS: Data of 773 patients who underwent HoLEP for BPO between 2010 and 2018 in a referral center were analyzed. Exclusion criteria were PCa detection in the HoLEP specimen or absence of post-operative PSA values. Patients were divided in a PCa group and Control group depending on whether or not PCa was detected during follow-up after HoLEP. The predictive value for future diagnosis of PCa of different forms of PSA-change after HoLEP was analyzed by multivariate Cox regression and ROC analysis. RESULTS: Overall, 24 (4.2%) patients developed PCa after HoLEP. At 5 year follow-up, the PCa-free survival rate was 85%. First post-operative PSA was an independent predictor of PCa diagnosis after HoLEP (HR 1.106, 95% CI 1.074-1.139, p < 0.001, ROC AUC 0.903) with an optimal cut-off value of 1.73 ng/ml (sensitivity 83.3%, specificity 82.3%). CONCLUSIONS: For patients who underwent HoLEP for BPO, post-operative PSA after HoLEP is an independent predictor for future PCa diagnosis. When PSA is > 1.73 ng/ml within the first year after HoLEP, rigorous follow-up and diagnostic investigations for PCa are indicated.

Three-dimensional assessment of umbilical vein deviation angle for prediction of liver herniation in left-sided congenital diaphragmatic hernia.

OBJECTIVES: To introduce a new sonographic marker of intrathoracic liver herniation in fetuses with left-sided congenital diaphragmatic hernia (CDH). METHODS: In a consecutive series of fetuses with isolated CDH, an ultrasound volume of the fetal abdomen was acquired. On this volume, offline calculation of the angle formed by the midline of the abdomen (joining the center of the vertebral body to the abdominal insertion of the umbilical cord) and a second line joining the center of the vertebral body to the intra-abdominal convexity of the umbilical vein was carried out to give the umbilical vein deviation angle (UVDA). The UVDA was measured in a group of normal fetuses selected as controls. At follow-up, the presence of liver herniation was investigated in all cases of CDH. UVDA values were compared between the CDH group and controls, and between CDH 'liver-up' vs 'liver-down' cases. A receiver-operating characteristics (ROC) curve was constructed to identify a cut-off value of the UVDA with the highest accuracy in predicting liver herniation in the CDH group. RESULTS: Between 2009 and 2015, 22 cases of left-sided CDH were included in the study group, of which nine cases had liver herniation. Eighty-eight normal fetuses were recruited as controls. The UVDA was significantly higher in the cases vs controls (15.25 ± 7.91° vs 7.68 ± 1.55°; P < 0.0001). Moreover, the UVDA was significantly increased in CDH fetuses with liver-up vs liver-down (21.77 ± 8.79° vs 10.75 ± 2.10°; P < 0.0001). On ROC curve analysis the UVDA showed good prediction of liver herniation (area under the ROC curve, 0.94; P < 0.0001) with the best cut-off of 15.2°, yielding a sensitivity of 89% and a specificity of 100% (P < 0.0001). CONCLUSIONS: In fetuses with CDH, umbilical vein bowing may be quantified by measuring the UVDA using three-dimensional ultrasound. This sonographic marker seems to be an accurate predictor of liver herniation in left-sided CDH. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Development of a patient-reported outcome measure for upper limb function in Duchenne muscular dystrophy: DMD Upper Limb PROM.

AIM: To develop a patient-reported outcome measure (PROM) assessing upper limb function related to activities of daily living (ADL) that cannot be observed in a clinical setting, specifically for patients with Duchenne muscular dystrophy (DMD) across a wide age range, applicable in the different stages of the disease. METHOD: The developmental process was based on US Food and Drug Administration guidelines. This included item generation from a systematic review of existing tools and expert opinion on task difficulty and relevance, involving individuals with DMD. Cultural aspects affecting ADL were taken into consideration to make this tool applicable to the broad DMD community. Items were selected in relation to a conceptual framework reflecting disease progression covering the full range of upper limb function across different ADL domains. RESULTS: After pilot testing and iterative Rasch analyses, redundant or clinically irrelevant items were removed. The final questionnaire consists of 32 items covering four domains of ADL (food, self-care, household and environment, leisure and communication). Test-retest reliability was excellent. INTERPRETATION: A DMD-specific upper limb PROM was developed on the basis of clinical relevance and psychometric robustness. Its main purpose is to document the patient self-reported natural history of DMD and assess the efficacy of interventions.

Importance of molecular biology in the characterization of beta-thalassemia carriers.

OBJECTIVES: The term beta-thalassemia includes all those hereditary disturbances of the hemoglobin (Hb), transferred trough a recessive autosomal mechanism, due to a reduced or else defective synthesis of beta globin sequences. The aim of this paper is to highlight as sometimes the only biochemical diagnosis is not exhaustive and a molecular diagnostic widening is necessary to detect the genetic deficiency that is the reason of the beta-thalassemic trait. CASE REPORT AND RESULTS: To improve this theory the following clinical case is reported: a 29 years old girl that was 11 weeks pregnant addressed us to receive the prenatal screening test related to the first three-month pregnancy period. The biochemical and hematological tests highlighted that Mrs. D.F. was a carrier of the beta-thalassemic trait, (MCV 63fl decrease, MCH 30pg, HbA2: 4.4 increase, HbF:1.5 increase, red blood cells 5.92 x 10(6)/ul and Hb 12.4 g/dl), that has been confirmed trough our molecular analysis (genotype: beta+IVS1.110 G --> A in heterozigosys). More difficult to be realized was the case of Mr. B.A.: he showed an uncertain hematological picture labeled as "compatible with a alpha-thalassemia picture" (MCV 62.9fl decrease, MCH 21.4pg decrease, HbA2: 2.7, HbF: 1.0, red blood cells 5.33 x10(6)/ul, Hb 11.4 g/dl decrease). This picture revealed difficult to be understood because of the regularity of HbA2 (2.7%) that was in contrast with the value of the MCV (62.9). In situation like this only the molecular diagnosis allows correctly highlighting the specific typology of thalassemia the subject is carrier of. As a matter of fact the molecular analysis excluded the possibility that Mr. B.A. was a alpha-thalassemia carrier and pointed out that he was a healthy carrier of beta-thalassemia (genotype beta degrees 39C --> T in heterozigosys). In the light of what has been explained above, the couple has been informed about risks to beget child suffering from beta-thalassemia and together with the married couple has been decided to work out a prenatal diagnosis through a sample of chorionic villus. DISCUSSION AND CONCLUSIONS: The identification of these particular cases fixes important implications about the prenatal diagnosis approach. The correct characterization of the healthy carrier is absolutely necessary with a subsequent study in depth of the partner's situation. It is important to highlight the importance of a careful study of hematological parameters and a widespread and correct information about clinical implication connected to the complications of the beta-thalassemia. As to this subject, the molecular study of the defect of the gene let to point out couples that run the risk of beta-thalassemia and to develop an exhaustive and correct information about the possibility to beget children suffering from beta-thalassemia. If two carrier partners wish to have children they can chose among the following possibilities: they can be well informed about the risk and accept the possibility to beget a child suffering from beta-thalassemia, they can give up the idea of having children or they can decide to beget children however but to avoid the possibility that the same suffers of thalassemia they can ask for a prenatal diagnosis.

Surgical technique to avoid bladder flap formation during cesarean section.

Cesarean section (CS) is now the most common major surgical procedure performed on women worldwide. A CS can be performed by either suturing or not suturing of the visceral peritoneum. Creation of the bladder flap is an integral step of the standard cesarean section. The bladder flap is made by superficially incising and dissecting the peritoneal lining to separate the urinary bladder from the lower uterine segment. It's still debated whether the formation of bladder flap is advantageous or not. If the uterine incision is made slightly above the vesicouterine peritoneal fold, the loose connective tissue between the uterus and the urinary bladder allows spontaneous descent of the bladder. Evidence on the role of the bladder flap in cesarean section is very limited. At present, it remains to be established whether there is any advantage in dissecting the bladder from the lower uterine segment during cesarean section.

Androgen insensitivity syndrome (or Morris syndrome) and other associated pathologies.

BACKGROUND: The androgen insensitivity syndrome (AIS) is a disease connected with the inactivation of AR due to a mutation that inactivate male sexual differentiation, and causes a spectrum of phenotypic anomalies having as a common aspect the loss of reproductive characteristics. PATIENTS: In this paper the clinical, endocrinological and molecular features of three patients are reported. The first case concerns a 17 years old patient, the second an infant suffering from inguinal hernia that has been surgically corrected when he was 3 months old and finally the third case concerns a 57 years old woman. RESULTS: All the subjects had a common primary amenorrhea and a following pelvic echography highlighted the absence of internal genital organs and the presence of a dead-end vagina. All the patients are characterized by a normal male karyotype and present on the short arm of the Y chromosome the SRY gene. Moreover, FISH revealed the presence of androgen receptor gene on the X chromosome and the SRY gene on the Y one. The automatic sequencing of the genes for the androgen receptor (AR) shows that each subject has a mutation in the gene for the androgen receptor (AR). These mutations are associated with complete androgen insensivity syndrome (CAIS). All the cases of study exhibited a negative family history for CAIS. CONCLUSION: This study confirms the need to perform a pelvic examination by means of echography in pre-pubertal and pubertal age to highlight the normality of the internal genitalia (uterus and ovaries). If a primary amenorrhea is checked, the karyotyping is compulsory. If a Morris's syndrome is suspected, it is of critical importance to find the rudimentary male gonads (by means of MRI, pelvic echography, laparoscopy) and surgically remove them to prevent the onset of malignancies (teratoblastoma, gonadoblastoma). Once the considered disease has been identified, a continuous psychological help can be considered useful for the patient and the family.

Adherence to Guideline Recommendations for Perioperative Chemotherapy in Patients with pN2-3 M0 Squamous Cell Carcinoma of the Penis: Temporal Trends and Survival Outcomes.

AIMS: To analyse contemporary perioperative chemotherapy (CHT) guideline adherence rates for pN2-3 M0 squamous cell carcinoma of the penis, as well as CHT association with cancer-specific (CSM) and other-cause mortality (OCM). MATERIALS AND METHODS: Within the Surveillance, Epidemiology, and End Results databases, 311 pN2-3 M0 squamous cell carcinoma of the penis patients treated with inguinal lymph node dissection were identified. Univariable and multivariable logistic regression analyses focused on CHT rates, whereas cumulative incidence plots and multivariable competing risks regression analyses tested for CSM and OCM rates. RESULTS: CHT was administered to 140 (45%) patients and rates increased from 37.5 to 62.2% (2004-2015; P = 0.02). Specifically, annual CHT rates increased over time in patients younger or equal to 65 years and in patients older than 65 years (44.4-84.6% versus 28.6-50%, respectively), but this trend was not statistically significant (P = 0.1 and P = 0.2, respectively). The median follow-up was 13 months for both CHT (interquartile range 8.0-32.2) and no-CHT subgroups (interquartile range 5.0-40.0). In multivariable logistic regression analyses, more contemporary year of diagnosis interval (odds ratio 2.08, P < 0.01) and age older than 75 years (odds ratio 0.14, P < 0.001) were independent predictors of CHT use. In multivariable competing risks regression analyses, CHT use did not affect CSM (hazard ratio 1.02; P = 0.7) or OCM (hazard ratio 1.56; P = 0.8). CONCLUSIONS: CHT adherence rates sharply increased in the most recent years. Despite this increase over time, the lack of efficacy regarding CSM benefit is disappointing.

[Melorheostosis linear scleroderma with osteopoikilosis. Description of a clinical case]. / Sclerodermia lineare meloreostotica con osteopecilia. Descrizione di un caso clinico.

A case of melorheostosis with osteopoikilosis and linear scleroderma is reported. The authors emphasize the rarity of the disease, the complexity of the therapeutic approach to the patient.

Hammersmith Functional Motor Scale and Motor Function Measure-20 in non ambulant SMA patients.

The aim of this prospective longitudinal multi centric study was to evaluate the correlation between the Hammersmith Functional Motor Scale and the 20 item version of the Motor Function Measure in non ambulant SMA children and adults at baseline and over a 12 month period. Seventy-four non-ambulant patients performed both measures at baseline and 49 also had an assessment 12 month later. At baseline the scores ranged between 0 and 40 on the Hammersmith Motor function Scale and between 3 and 45 on the Motor Function Measure 20. The correlation between the two scales was 0.733. The 12 month changes ranged between -11 and 4 for the Hammersmith and between -11 and 7 for the Motor Function Measure 20. The correlation between changes was 0.48. Our results suggest that both scales provide useful information although they appeared to work differently at the two extremes of the spectrum of abilities. The Hammersmith Motor Function Scale appeared to be more suitable in strong non ambulant patients, while the Motor Function Measures appeared to be more sensitive to capture activities and possible changes in the very weak patients, including more items capturing axial and upper limb activities. The choice of these measures in clinical trials should therefore depend on inclusion criteria and magnitude of expected changes.

Six minute walk test in type III spinal muscular atrophy: a 12month longitudinal study.

The aim of our longitudinal multicentric study was to establish the changes on the 6min walk test (6MWT) in ambulant SMA type III children and adults over a 12month period. Thirty-eight ambulant type III patients performed the 6MWT at baseline and 12months after baseline. The distance covered in 6min ranged between 75 and 510m (mean 294.91, SD 127) at baseline and between 50 and 611m (mean 293.41m, SD 141) at 12months. The mean change in distance between baseline and 12months was -1.46 (SD 50.1; range: -183 to 131.8m). The changes were not correlated with age or baseline values (p>.05) even though younger patients reaching puberty, had a relatively higher risk of showing deterioration of more than 30m compared to older patients. Our findings provide the first longitudinal data using the 6MWT in ambulant SMA patients.

Functional changes in Duchenne muscular dystrophy: a 12-month longitudinal cohort study.

OBJECTIVE: The aim of the study was to assess different outcome measures in a cohort of ambulant boys with Duchenne muscular dystrophy (DMD) over 12 months in order to establish the spectrum of possible changes in relation to age and steroid treatment. METHODS: The study is a longitudinal multicentric cohort study. A total of 106 ambulant patients with DMD were assessed using the 6-minute walk test (6MWT) and North Star Ambulatory Assessment (NSAA) at baseline and 12 months. Clinical data including age and steroid treatment were collected. RESULTS: During the 12 months of the study, we observed a mean decline of 25.8 meters in the 6MWT with a SD of 74.3 meters. On NSAA, the mean decline was 2.2 points with a SD of 3.7. Not all the boys with DMD in our cohort showed a decline over the 12 months, with young boys showing some improvement in their 6MWT and NSAA scores up to the age of 7. NSAA and the 6MWT had the highest correlation (r = 0.52, p < 0.001). CONCLUSIONS: This study provides longitudinal data of NSAA and 6MWT over a 12-month period. These data can be useful when designing a clinical trial.

The Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND): test development and reliability.

The motor skills of patients with spinal muscular atrophy, type I (SMA-I) are very limited. It is difficult to quantify the motor abilities of these patients and as a result there is currently no validated measure of motor function that can be utilized as an outcome measure in clinical trials of SMA-I. We have developed the Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders ("CHOP INTEND") to evaluate the motor skills of patients with SMA-I. The test was developed following the evaluation of 26 infants with SMA-I mean age 11.5 months (1.4-37.9 months) with the Test of Infant Motor Performance and The Children's Hospital of Philadelphia Test of Strength in SMA, a newly devised motor assessment for SMA. Items for the CHOP INTEND were selected by an expert panel based on item mean and standard deviation, item frequency distribution, and Chronbach's alpha. Intra-rater reliability of the resulting test was established by test-retest of 9 infants with SMA-I over a 2 month period; Intraclass correlation coefficient (ICC) (3,1)=0.96. Interrater reliability was by video analysis of a mixed group of infants with neuromuscular disease by 4 evaluators; ICC (3,4)=0.98 and in a group of 8 typically developing infants by 5 evaluators ICC (3,5)=0.93. The face validity of the CHOP INTEND is supported by the use of an expert panel in item selection; however, further validation is needed. The CHOP INTEND is a reliable measure of motor skills in patients with SMA-I and neuromuscular disorders presenting in infancy.

Reliability of the North Star Ambulatory Assessment in a multicentric setting.

The aim of this study was to investigate the suitability of the North Star Ambulatory Assessment as a possible outcome measure in multicentric clinical trials. More specifically we wished to investigate the level of training needed for achieving a good interobserver reliability in a multicentric setting. The scale was specifically designed for ambulant children with Duchenne Muscular Dystrophy and includes 17 items that are relevant for this cohort. Thirteen Italian centers participated in the study. In the first phase of the study we provided two training videos and an example of the scale performed on a child. After the first session of training, all the 13 examiners were asked to send a video with an assessment performed in their centre and to score all the videos collected. There were no difficulties in performing the items and in obtaining adequate videos with a hand held camera but the results showed a poor interobserver reliability (<.5). After a second training session with review and discussion of the videos previously scored, the same examiners were asked to score three new videos. The results of this session had an excellent interobserver reliability (.995). The level of agreement was maintained even when the same videos were rescored after a month, showing a significant intra-observer reliability (.95). Our results suggest that the NSAA is a test that can be easily performed, completed in 10 min and can be used in a multicentric setting, providing that adequate training is administered.

Pemphigus vulgaris following cobalt therapy for bronchial carcinoma.

A 52-year-old male patient with bronchial carcinoma developed pemphigus vulgaris 3 weeks after the end of cobalt therapy. The possible role of gamma-radiation in inducing the skin disease is discussed.

Use and nursing of the helmet in delivering non invasive ventilation.

Continuous positive end-expiratory pressure (CPAP) and Pressure Support Ventilation (PSV) are commonly used for the therapy of several forms of respiratory failure. CPAP and PSV can be delivered both during invasive respiratory treatment, by means of an endotracheal tube or tracheostomy, and during non invasive respiratory treatment. Non Invasive Ventilation (NIV) is commonly used for the therapy of several forms of respiratory failure (COPD, Weaning period from Invasive Mechanical Ventilation, Cardiogenic Edema,.) and the helmet could be a good new device to deliver it with a better compliance instead the common facial mask without increasing the nurses' workload.