Automatic identification and segmentation of slice of minimal hiatal dimensions in transperineal ultrasound volumes.

OBJECTIVE: To develop and validate a tool for automatic selection of the slice of minimal hiatal dimensions (SMHD) and segmentation of the urogenital hiatus (UH) in transperineal ultrasound (TPUS) volumes. METHODS: Manual selection of the SMHD and segmentation of the UH was performed in TPUS volumes of 116 women with symptomatic pelvic organ prolapse (POP). These data were used to train two deep-learning algorithms. The first algorithm was trained to provide an estimation of the position of the SMHD. Based on this estimation, a slice was selected and fed into the second algorithm, which performed automatic segmentation of the UH. From this segmentation, measurements of the UH area (UHA), anteroposterior diameter (APD) and coronal diameter (CD) were computed automatically. The mean absolute distance between manually and automatically selected SMHD, the overlap (dice similarity index (DSI)) between manual and automatic UH segmentation and the intraclass correlation coefficient (ICC) between manual and automatic UH measurements were assessed on a test set of 30 TPUS volumes. RESULTS: The mean absolute distance between manually and automatically selected SMHD was 0.20 cm. All DSI values between manual and automatic UH segmentations were above 0.85. The ICC values between manual and automatic UH measurements were 0.94 (95% CI, 0.87-0.97) for UHA, 0.92 (95% CI, 0.78-0.97) for APD and 0.82 (95% CI, 0.66-0.91) for CD, demonstrating excellent agreement. CONCLUSIONS: Our deep-learning algorithms allowed reliable automatic selection of the SMHD and UH segmentation in TPUS volumes of women with symptomatic POP. These algorithms can be implemented in the software of TPUS machines, thus reducing clinical analysis time and simplifying the examination of TPUS data for research and clinical purposes. © 2021 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Vaginal laxity: which measure of levator ani distensibility is most predictive?

OBJECTIVE: To assess the predictive value of measures of levator hiatal distension at rest and on maximum Valsalva maneuver for symptoms of vaginal laxity. METHODS: This was a retrospective study of women seen at a tertiary urogynecological unit. All women underwent a standardized interview, clinical examination and four-dimensional translabial ultrasound examination. Area, anteroposterior diameter (APD) and coronal diameter (CD) of the levator hiatus were measured at rest and on maximum Valsalva maneuver in the plane of minimal hiatal dimensions using the rendered volume technique, by an operator blinded to all clinical data. The association between levator hiatal measurements and vaginal laxity was assessed, and receiver-operating-characteristics (ROC)-curve analysis was used to determine their predictive value. RESULTS: Data from 490 patients were analyzed. Mean age was 58 (range, 18-88) years, and vaginal laxity was reported by 111 (23%) women. Measurements obtained on maximum Valsalva were significantly larger in women who reported vaginal laxity than in those who did not, with mean levator hiatal area, APD and CD of 30.45 ± 8.74 cm2 , 7.24 ± 1.16 cm and 5.60 ± 0.89 cm, respectively, in the vaginal-laxity group, compared with 24.84 ± 8.63 cm2 , 6.64 ± 1.22 cm and 5.01 ± 0.97 cm in the no-laxity group (P < 0.001 for all). Measurements obtained at rest were not significantly different between the groups. Multiple logistic regression analysis controlling for age, body mass index, vaginal parity and levator avulsion confirmed these results. The best regression model for the prediction of vaginal laxity included age, vaginal parity and levator hiatal area on maximum Valsalva. ROC-curve analysis of levator hiatal measurements on maximum Valsalva in the prediction of vaginal laxity demonstrated areas under the curve of 0.68 (95% CI, 0.63-0.73) for area, 0.63 (95% CI, 0.57-0.68) for APD and 0.68 (95% CI, 0.62-0.73) for CD. CONCLUSIONS: Levator hiatal area on maximum Valsalva seems to be the measure of levator ani distensibility that is most predictive of symptoms of vaginal laxity. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Ficopomatus enigmaticus larval development assay: An application for toxicity assessment of marine sediments.

Ficopomatus enigmaticus is a serpulid polychaete, reef-forming, dioecious gamete spawner throughout different seasons and in different salinity conditions. Due to these characteristics, its candidacy as a model organism to monitor both marine and brackish matrices was assessed. Marine sediments collected in a polluted area near the port of Ancona (Italy) were used as case study. Besides the chemical characterization of sediments, the larval development of F. enigmaticus was adopted as an assay for ecotoxicological assessment of sediments in addition to a regulatory bioassay battery with different organisms and endpoints. The quality of sediments was classified according to the Italian Ministerial Decree for sediment management (Ministerial Decree 173, 2016) by using the SEDI-QUAL-SOFT® (ver. 109.0) software developed by the Italian Environmental Protection Agency (ISPRA). The F. enigmaticus larval development assay showed a quite similar sensitivity to C. gigas larval development assays, indicating its potential use in a regulatory battery of bioassays.

Paraneoplastic rheumatic disorders: a narrative review.

Paraneoplastic syndromes (PS) are a heterogeneous group of diseases related to a neoplasm, indirectly dependent on it. Diagnosis and the treatment are often a challenge for clinicians, not least because the pathogenetic mechanisms are highly complex and not entirely known. Nonetheless, in most cases, PS precede the diagnosis of malignancies, thus their identification is particularly important in addressing physicians' diagnostic work-up with regard to early cancer diagnosis. Among paraneoplastic syndromes, those of rheumatologic interest represent a large component. In this paper, we review the main rheumatic PS.

Prevalence and incidence of osteoporotic fractures in patients on long-term glucocorticoid treatment for rheumatic diseases: the Glucocorticoid Induced OsTeoporosis TOol (GIOTTO) study.

Osteoporosis and fractures are common and invalidating consequences of chronic glucorticoid (GC) treatment. Reliable information regarding the epidemiology of GC induced osteoporosis (GIOP) comes exclusively from the placebo group of randomized clinical trials while observational studies are generally lacking data on the real prevalence of vertebral fractures, GC dosage and primary diagnosis. The objective of this study was to evaluate the prevalence and incidence of osteoporotic fractures and to identify their major determinants (primary disease, GC dosage, bone mineral density, risk factors, specific treatment for GIOP) in a large cohort of consecutive patients aged >21 years, on chronic treatment with GC (≥5 mg prednisone - PN - equivalent) and attending rheumatology centers located all over Italy. Glucocorticoid Induced OsTeoporosis TOol (GIOTTO) is a national multicenter cross-sectional and longitudinal observational study. 553 patients suffering from Rheumatoid Arthritis (RA), Polymyalgia Rheumatica (PMR) and Connective Tissue Diseases (CTDs) and in chronic treatment with GCs were enrolled. Osteoporotic BMD values (T score <-2.5) were observed in 28%, 38% and 35% of patients with CTDs, PMR or RA at the lumbar spine, and in 18%, 29% and 26% at the femoral neck, respectively. Before GC treatment, prevalent clinical fractures were reported by 12%, 37% and 17% of patients with CTDs, PMR, or RA, respectively. New clinical fragility fractures during GC treatment were reported by 12%, 10% and 23% of CTDs, PMR and RA patients, respectively. Vertebral fractures were the prevailing type of fragility fracture. More than 30% of patients had recurrence of fracture. An average of 80% of patients were in supplementation with calcium and/or vitamin D during treatment with GCs. Respectively, 64%, 80%, and 72% of the CTDs, PMR and RA patients were on pharmacological treatment for GIOP, almost exclusively with bisphosphonates. The GIOTTO study might provide relevant contributions to clinical practice, in particular by highlighting and quantifying in real life the prevalence of GIOP and relative fractures, the frequency of the main risk factors, and the currently sub-optimal prevention. Moreover, these results emphasize the importance of the underlying rheumatic disease on the risk of GIOP associated fractures.

Serum 25-OH vitamin D levels in systemic sclerosis: analysis of 140 patients and review of the literature.

Hypovitaminosis D is increasingly reported in autoimmune diseases. We investigated the 25-OH-vitamin D (25-OH-vitD) levels in systemic sclerosis (SSc) patients, in correlation with disease's features. We measured the 25-OH-vitD serum levels in 140 consecutive patients (F/M 126/15; mean age 61 ± 15.1 years), 91 without (group A) and 49 with (group B) 25-OH-cholecalciferol supplementation. Patients of group A invariably showed low 25-OH-vitD levels (9.8 ± 4.1 ng/ml vs. 26 ± 8.1 ng/ml of group B); in particular, 88/91 (97%) patients showed vitamin D deficiency (<20 ng/ml), with very low vitamin D levels (<10 ng/ml) in 40 (44%) subjects. Only 15/49 (30.6%) patients of group B reached normal levels of 25-OH-vitD (≥30 ng/ml), whereas vitamin D deficiency persisted in 12/49 (24.5%) individuals. Parathormone levels inversely correlated with 25-OH-vitD (r = -0.3, p < 0.0001). Of interest, hypovitaminosis D was statistically associated with autoimmune thyroiditis (p = 0.008), while calcinosis was more frequently observed in patients of group A (p = 0.057). Moreover, we found significantly higher percentage of serum anticentromere antibodies in group B patients with 25-OH-vitD level ≥30 ng/ml (8/15 vs. 6/34; p = 0.017). In literature, hypovitaminosis D is very frequent in SSc patients. An association with disease duration, calcinosis, or severity of pulmonary involvement was occasionally recognized. Hypovitaminosis D is very frequent in SSc and severe in a relevant percentage of patients; furthermore, less than one third of supplemented subjects reached normal levels of 25-OH-vitD. The evaluation of 25-OH-vitD levels should be included in the routine clinical work-up of SSc. The above findings expand previous observations and may stimulate further investigations.

A multi-centre, open label, long-term follow-up study to evaluate the benefits of a new viscoelastic hydrogel (Hymovis®) in the treatment of knee osteoarthritis.

OBJECTIVE: To evaluate the long-term efficacy and safety of Hymovis® in the symptomatic treatment of knee osteoarthritis (OA). PATIENTS AND METHODS: This is a prospective, multi-center, open label, phase III clinical study. Two intra-articular injections (3 mL) of Hymovis® (8 mg/mL HYADD® 4) were administered 1 week apart at the beginning of the study on day 0 and day 7 and after 6 months from baseline, on day 182 and 189. Follow-up assessment were conducted for 52 weeks. 50 subjects, > 40 years old, with knee OA, with clinical and radiological confirm, complain pain in the target knee were enrolled. The variables considered were: WOMAC questionnaire, Joint Space Width (JSW), OMERACT OARSI responder criteria, EQ-5D questionnaire, rescue medication consumption. RESULTS: After the injections of Hymovis®, pain perceived by the patient when walking on a flat surface (WOMAC A1 score) significantly improves at the end of the study respect to the baseline. WOMAC stiffness, physical function and total score significantly improve during the study since 3 months after treatment, and it is maintained up to the end of the study (p < 0.001). By the x-ray analysis of knee, a radiological progression of OA was observed in the 26% of patients at the end of the study, while 88% of patients result to be responder to the therapy classified as per OMERACT-OARSI criteria. The EQ-5D weighted index increased significantly, against baseline, at each study time point (p < 0.001). Investigator's and patient's global assessment of the disease measured by the VAS both show a marked improvement in patient's health conditions. CONCLUSIONS: Results from this study confirm that Hymovis® alleviate the knee pain since the first treatment cycle. The patients treated with two cycles of intra-articular injections of Hymovis® have a progressive pain reduction that is maintained up to one year after the treatment start with improve of all the scores considered in this study. Hymovis® is effective and safe in symptomatic treatment of painful knee OA.

Lung involvement in systemic sclerosis: role of high resolution computed tomography and its relationship with other pulmonary and clinico-serological features.

The study investigated the characteristic of interstitial lung disease in a large series of systemic sclerosis (SSc) patients by means of HRCT and the correlations between functional lung parameters, serological features and the extent of lung involvement evaluated by high-resolution computed tomography (HRCT). One hundred and seven SSc patients, consecutively investigated by means of HRCT, standard chest X-ray, and pulmonary function tests, were retrospectively evaluated. Chest radiogram and HRCT scores were strongly associated (Pearson’'s r=0.82, p < .0001); moreover, the first significantly correlated with spirometric parameters, even if weakly. Anti-Scl70 and anti-centromere antibodies were associated with higher (p=0.01) and lower HRCT score (p=0.0002), respectively. The extension of interstitial lung involvement in SSc evaluated with HRCT is directly proportional to functional lung parameters. HRCT, spirometry and DLco should be considered essential in the core-set of non-invasive diagnostic tools for the first-line assessment of scleroderma lung involvement.

Unusual association between Budd-Chiari syndrome secondary to antiphospholipid syndrome and relapsing polychondritis: a case report and review of the literature.

Relapsing polychondritis is a rare immune-mediated condition, characterized by episodic inflammation of the cartilaginous tissue, in particular the ears, nose, and eyes, and involvement of joints and respiratory tract. Nearly one third of patients showed other associated diseases, such as systemic vasculitides, connective tissue diseases, or myelodysplastic syndromes. Antiphospholipid antibodies can be found in relapsing polychondritis in patients with no clinical thrombotic disease. However, when antiphospholipid syndrome is present, its clinical manifestations can be severe and life threatening. We describe the case of a patient with relapsing polychondritis associated to Budd-Chiari syndrome due to antiphospholipid syndrome. The present clinical observations together with the updated review of the literature suggest a search for antiphospholipid antibodies in all patients with relapsing polychondritis.

The pathogenesis of the anaemia of chronic disorders.

Anemia of chronic disorders is a typical condition of infective, immunological and neoplastic diseases. Hepcidin and proinflammatory cytokines play a leading role in its pathogenesis. Hepcidin is a hormone produced by the liver that controls iron metabolism. It ensures that iron is retained by enterocytes (where the metal is absorbed) and by macrophages (that store the iron that results from the physiological breakdown of erythrocytes). Cytokines play a role in hepcidin synthesis, and in the proliferation and the maturation of the erythroid components within bone marrow. This paper discusses the pathogenetic mechanisms of anemia in chronic disorders.

D-penicillamine in the treatment of eosinophilic fasciitis: case reports and review of the literature.

Eosinophilic fasciitis (EF) is a rare disease characterized by symmetrical thickness and hardening of the skin, especially localized to forearms and thorax, with eosinophilia. Corticosteroids represent the first-line therapy, even if some patients are scarcely responsive and/or may develop important side effects due to long-term treatment. Here, we describe three cases of EF, two of them refractory to previous steroid therapy, successfully treated with D-penicillamine. The present clinical observations together with the updated review of the literature suggest usefulness of D-penicillamine in EF patients, as well as its potential steroid-sparing value.

Comparison of ambulatory and polysomnographic recording of jaw muscle activity during sleep in normal subjects.

Clinicians and investigators need a simple and reliable recording device to diagnose or monitor sleep bruxism (SB). The aim of this study was to compare recordings made with an ambulatory electromyographic telemetry recorder (TEL-EMG) with those made with standard sleep laboratory polysomnography with synchronised audio-visual recording (PSG-AV). Eight volunteer subjects without current history of tooth grinding spent one night in a sleep laboratory. Simultaneous bilateral masseter EMG recordings were made with a TEL-EMG and standard PSG. All types of oromotor activity and rhythmic masseter muscle activity (RMMA), typical of SB, were independently scored by two individuals. Correlation and intra-class coefficient (ICC) were estimated for scores on each system. The TEL-EMG was highly sensitive to detect RMMA (0·988), but with low positive predictive value (0·231) because of a high rate of oromotor activity detection (e.g. swallowing and scratching). Almost 72% of false-positive oromotor activity scored with the TEL-EMG occurred during the transient wake period of sleep. A non-significant correlation between recording systems was found (r = 0·49). Because of the high frequency of wake periods during sleep, ICC was low (0·47), and the removal of the influence of wake periods improved the detection reliability of the TEL-EMG (ICC = 0·88). The TEL-EMG is sensitive to detect RMMA in normal subjects. However, it obtained a high rate of false-positive detections because of the presence of frequent oromotor activities and transient wake periods of sleep. New algorithms are needed to improve the validity of TEL-EMG recordings.

[Percutaneous vertebroplasty as therapy for vertebral fractures: results in a series of osteoporotic patients]. / Trattamento delle fratture vertebrali con vertebroplastica percutanea: risultati in una casistica di pazienti osteoporotici.

In the recent years, percutaneous vertebroplasty is available for the treatment of the vertebral fractures, primarily to relieve pain related to the lesion. In order to evaluate the efficacy and the safety of this technique, we have treated with percutaneous vertebroplasty, using polymethylmethacrylate, 22 patients, affected by one or more vertebral fractures caused by osteoporosis. All the patients satisfied the inclusion criteria of the American College of Radiology for percutaneous vertebroplasty. These patients were compared with a control group of 23 not treated subjects with vertebral fractures, using questionnaires for assessment of pain and quality of life, drug intake, use of corset, and tolerability of the surgery. In the large majority of patients, the treatment of osteoporotic vertebral fractures with percutaneous vertebroplasty resulted in a prompt, marked and sustained relief of vertebral pain with a persistent improvement of quality of life.

[Dactilitis and oligoarthritis after BCG immunotherapy in a patient affected by bladder cancer]. / Dattilite ed oligoartrite secondarie ad immunoterapia con BCG in un paziente con carcinoma vescicale.

The treatment of bladder cancer with Bacillus of Calmette-Guerin (BCG) immunotherapy can induce the appearance of a reactive disorder. The Authors describe a 55-year-old male patient with bladder cancer treated with endovesical instillation of BCG immunotherapy, followed after the fifth application by asymmetric oligoarthritis and dactilitis. The observed positivity of both HLA-B27 and HLA-B51 antigens reinforces the hypothesis of a reactive form, possibly through "molecular mimicry" mechanism. The discontinuation of BCG instillation along which a therapeutic attempt with NSAD failed to improve the rheumatic manifestation, which completely remitted after a four-month course of oral steroids. No relapses of joint and tendon involvement was observed during the following five-month period. The clinico-pathogenetic implications suggested by this case are discussed.

[Diffuse post-traumatic calcification of the anterior longitudinal ligamentum of cervical and dorsal spine]. / Diffusa calcificazione post-traumatica del legamento longitudinale anteriore a livello cervico-dorsale.

Among the different conditions causing inflammation and calcification/ossification of the soft tissues of the spinal cord, single or recurrent traumatic events are included. Within the international literature, the involvement of the posterior longitudinal ligament, following spinal cord injuries is frequently reported, especially in the elders. The Authors describe here an uncommon calcification/ossification of the anterior longitudinal ligament occurred after a double traumatic event in a young man, followed clinically and radiologically for a long-term period. On the basis of clinical, laboratory and radiological findings, the differential diagnosis with other possible aetiologies, especially DISH (Diffuse idiopathic skeletal hyperostosis) and ankylosing spondylitis, is discussed.

Quantitative polygraphic controlled study on efficacy and safety of oral splint devices in tooth-grinding subjects.

The efficacy of occlusal splints in diminishing muscle activity and tooth-grinding damage remains controversial. The objective of this study was to compare the efficacy and safety of an occlusal splint (OS) vs. a palatal control device (PCD). Nine subjects with sleep bruxism (SB) participated in this randomized study. Sleep laboratory recordings were made on the second night to establish baseline data. Patients then wore each of the splints in the sleep laboratory for recording nights three and four, two weeks apart, according to a crossover design. A statistically significant reduction in the number of SB episodes per hour (decrease of 41%, p = 0.05) and SB bursts per hour (decrease of 40%, p < 0.05) was observed with the two devices. Both oral devices also showed 50% fewer episodes with grinding noise (p = 0.06). No difference was observed between the devices. Moreover, no changes in respiratory variables were observed. Both devices reduced muscle activity associated with SB.

Double-blind, crossover, placebo-controlled trial of bromocriptine in patients with sleep bruxism.

This study was designed to assess the effects of bromocriptine, a dopamine D2 receptor agonist, on sleep bruxism. Seven otherwise healthy patients with severe and frequent sleep bruxism participated in this randomized, double-blind, placebo-controlled study. The study used a crossover design that included 2 weeks of active treatment or placebo with a washout period of 1 week. To further evaluate whether bromocriptine influences striatal D2 receptor binding, we used iodine-123-iodobenzamide single photon emission computed tomography (SPECT) under both placebo and bromocriptine regimens. Bromocriptine did not reduce the frequency of episodes of bruxism during sleep (mean +/- SEM, 9.0 +/- 1.0 and 9.6 +/- 1.5 bruxism episodes per hour for placebo and bromocriptine, respectively) or the amplitude of masseter muscle contractions (root mean square values, 48.2 +/- 15.5 microV and 46.9 +/- 12.7 microV for placebo and bromocriptine, respectively). SPECT also failed to reveal that either treatment had any influence on striatal D2 binding (values for total binding in counts/pixel, 1.80 [1.72-1.93] and 1.79 [1.56-1.87] for placebo and bromocriptine, respectively). This study shows that a nightly dose of bromocriptine does not exacerbate or reduce sleep bruxism motor activity.

Heart rate changes during sleep in response to experimental thermal (nociceptive) stimulations in healthy subjects.

OBJECTIVE: During wakefulness, nociceptive thermal stimulation can trigger a rapid and transient rise in heart rate (HR). During sleep, HR variations are different across sleep stages; HR is more variable in stage 2 and in REM than in stages 3 and 4. The aim of this study was to assess the HR response to experimental thermal stimulation during different sleep stages. METHODS: Eight young subjects free of sleep and pain problems, underwent a night of polysomnographic recording during which experimental thermal stimulations were applied. During all sleep stages (St), a series of cold, warm/control and heat pain stimulations were applied over the shoulder skin by means of a water-driven system. Variation of HR interval was measured for 6 s before and for 6 s during the thermal stimulation. RESULTS: In comparison to control warm stimulation, experimental nociceptive thermal stimulation induced a significant rise in HR during sleep; HR increased by 7% in St 2, 5.4% in St 3&4, and by 4.3% in REM sleep. CONCLUSION: The brief increase in cardiac activity with experimental nociceptive stimulation suggests that during sleep, the autonomic-cardiac nervous system remains reactive to external sensory inputs and is part of the physiological response to preserve body safety and sleep integrity in the face of potentially harmful stimulation.

Sleep arousal response to experimental thermal stimulation during sleep in human subjects free of pain and sleep problems.

Although the interaction between sleep and pain is generating considerable interest (NIH Technology Assessment Panel, 1996), it is still unknown if chronic pain is the cause or effect of poor sleep. To further this understanding, subjects free of pain and sleep problems need to be studied in order to assess their response to pain during sleep, defined as a behavioral and a physiological state in which sensory processing is altered. (For example, while auditory perception remains active, other sensory inputs are facilitated, attenuated, or suppressed (Velluti, 199746 degrees C) was statistically greater in the lighter sleep stage 2 (48.3%) than in the deeper stages 3&4 (27.9%). A nocifensive behavioral-motor response was associated with only 2.5% of the 351 heat pain stimuli. Two other markers of sleep quality-sleep stage shift and awakening-were not influenced by the thermal stimuli. None of the subjects demonstrated any burns in the morning following the thermal stimulations applied during sleep. We conclude that the processing of nociceptive inputs is attenuated across sleep stages.