Novel artificial intelligence approach for automatic differentiation of fetal occiput anterior and non-occiput anterior positions during labor.

OBJECTIVES: To describe a newly developed machine-learning (ML) algorithm for the automatic recognition of fetal head position using transperineal ultrasound (TPU) during the second stage of labor and to describe its performance in differentiating between occiput anterior (OA) and non-OA positions. METHODS: This was a prospective cohort study including singleton term (> 37 weeks of gestation) pregnancies in the second stage of labor, with a non-anomalous fetus in cephalic presentation. Transabdominal ultrasound was performed to determine whether the fetal head position was OA or non-OA. For each case, one sonographic image of the fetal head was then acquired in an axial plane using TPU and saved for later offline analysis. Using the transabdominal sonographic diagnosis as the gold standard, a ML algorithm based on a pattern-recognition feed-forward neural network was trained on the TPU images to discriminate between OA and non-OA positions. In the training phase, the model tuned its parameters to approximate the training data (i.e. the training dataset) such that it would identify correctly the fetal head position, by exploiting geometric, morphological and intensity-based features of the images. In the testing phase, the algorithm was blinded to the occiput position as determined by transabdominal ultrasound. Using the test dataset, the ability of the ML algorithm to differentiate OA from non-OA fetal positions was assessed in terms of diagnostic accuracy. The F1 -score and precision-recall area under the curve (PR-AUC) were calculated to assess the algorithm's performance. Cohen's kappa (κ) was calculated to evaluate the agreement between the algorithm and the gold standard. RESULTS: Over a period of 24 months (February 2018 to January 2020), at 15 maternity hospitals affiliated to the International Study group on Labor ANd Delivery Sonography (ISLANDS), we enrolled into the study 1219 women in the second stage of labor. On the basis of transabdominal ultrasound, they were classified as OA (n = 801 (65.7%)) or non-OA (n = 418 (34.3%)). From the entire cohort (OA and non-OA), approximately 70% (n = 824) of the patients were assigned randomly to the training dataset and the rest (n = 395) were used as the test dataset. The ML-based algorithm correctly classified the fetal occiput position in 90.4% (357/395) of the test dataset, including 224/246 with OA (91.1%) and 133/149 with non-OA (89.3%) fetal head position. Evaluation of the algorithm's performance gave an F1 -score of 88.7% and a PR-AUC of 85.4%. The algorithm showed a balanced performance in the recognition of both OA and non-OA positions. The robustness of the algorithm was confirmed by high agreement with the gold standard (κ = 0.81; P < 0.0001). CONCLUSIONS: This newly developed ML-based algorithm for the automatic assessment of fetal head position using TPU can differentiate accurately, in most cases, between OA and non-OA positions in the second stage of labor. This algorithm has the potential to support not only obstetricians but also midwives and accoucheurs in the clinical use of TPU to determine fetal occiput position in the labor ward. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

New technique for automatic sonographic measurement of change in head-perineum distance and angle of progression during active phase of second stage of labor.

OBJECTIVE: To evaluate the performance of a new ultrasound technique for the automatic assessment of the change in head-perineum distance (delta-HPD) and angle of progression (delta-AoP) during the active phase of the second stage of labor. METHODS: This was a prospective observational cohort study including singleton term pregnancies with fetuses in cephalic presentation during the active phase of the second stage of labor. In each patient, two videoclips of 10 s each were acquired transperineally, one in the axial and one in the sagittal plane, between rest and the acme of an expulsive effort, in order to measure HPD and AoP, respectively. The videoclips were processed offline and the difference between the acme of the pushing effort and rest in HPD (delta-HPD) and AoP (delta-AoP) was calculated, first manually by an experienced sonographer and then using a new automatic technique. The reliability of the automatic algorithm was evaluated by comparing the automatic measurements with those obtained manually, which was considered as the reference gold standard. RESULTS: Overall, 27 women were included. A significant correlation was observed between the measurements obtained by the automatic and the manual methods for both delta-HPD (intraclass correlation coefficient (ICC) = 0.97) and delta-AoP (ICC = 0.99). The high accuracy provided by the automatic algorithm was confirmed by the high values of the coefficient of determination (r2 = 0.98 for both delta-HPD and delta-AoP) and the low residual errors (root mean square error = 1.2 mm for delta-HPD and 1.5° for delta-AoP). A Bland-Altman analysis showed a mean difference of 0.52 mm (limits of agreement, -1.58 to 2.62 mm) for delta-HPD (P = 0.034) and 0.35° (limits of agreement, -2.54 to 3.09°) for delta-AoP (P = 0.39) between the manual and automatic measurements. CONCLUSIONS: The automatic assessment of delta-AoP and delta-HPD during maternal pushing efforts is feasible. The automatic measurement of delta-AoP appears to be reliable when compared with the gold standard manual measurement by an experienced operator. Copyright © 2020 ISUOG. Published by John Wiley & Sons Ltd.

Automatic ultrasound technique to measure angle of progression during labor.

OBJECTIVE: To evaluate the accuracy and reliability of an automatic ultrasound technique for assessment of the angle of progression (AoP) during labor. METHODS: Thirty-nine pregnant women in the second stage of labor, with fetus in cephalic presentation, underwent conventional labor management with additional translabial sonographic examination. AoP was measured in a total of 95 acquisition sessions, both automatically by an innovative algorithm and manually by an experienced sonographer, who was blinded to the algorithm outcome. The results obtained from the manual measurement were used as the reference against which the performance of the algorithm was assessed. In order to overcome the common difficulties encountered when visualizing by sonography the pubic symphysis, the AoP was measured by considering as the symphysis landmark its centroid rather than its distal point, thereby assuring high measurement reliability and reproducibility, while maintaining objectivity and accuracy in the evaluation of progression of labor. RESULTS: There was a strong and statistically significant correlation between AoP values measured by the algorithm and the reference values (r = 0.99, P < 0.001). The high accuracy provided by the automatic method was also highlighted by the corresponding high values of the coefficient of determination (r2 = 0.98) and the low residual errors (root mean square error = 2°27' (2.1%)). The global agreement between the two methods, assessed through Bland-Altman analysis, resulted in a negligible mean difference of 1°1' (limits of agreement, 4°29'). CONCLUSIONS: The proposed automatic algorithm is a reliable technique for measurement of the AoP. Its (relative) operator-independence has the potential to reduce human errors and speed up ultrasound acquisition time, which should facilitate management of women during labor. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

N-(4-hydroxyphenyl)retinamide promotes apoptosis of resting and proliferating B-cell chronic lymphocytic leukemia cells and potentiates fludarabine and ABT-737 cytotoxicity.

The in vitro effects of the synthetic retinoid N-(4-hydroxyphenyl)retinamide (4HPR, fenretinide) on primary B-cell chronic lymphocytic leukemia (CLL) cells from previously untreated CLL patients were investigated. 4HPR promoted the intrinsic apoptotic pathway by reactive oxygen species (ROS) generation and was accompanied by drop of Mcl-1 protein expression. The latter was not attributable to transcriptional downregulation but to protein degradation mediated by jun N-terminal kinase activation, and likely by NF-kB downregulation and Noxa upregulation. CLL cells stimulated in vitro with CD40L did not increase 4HPR chemoresistance if activation was accompanied by proliferation. Intra-patient analysis confirmed that the proliferating pool of CLL cells was more sensitive to the cytotoxic action of 4HPR than the activated but resting CLL subpopulation. The different 4HPR susceptibility of the two subpopulations was associated with higher Noxa expression in proliferating CLLs. Combination experiments revealed that 4HPR strongly potentiated ABT-737 cytotoxicity, especially in proliferating CLL cells that displayed amplified chemoresistance to ABT-737 alone. Synergic cytotoxicity was also demonstrated in combination with fludarabine, in both resting and stimulated CLL samples. This study entitles 4HPR to be assayed as a chemotherapeutic adjuvant for the treatment of CLL.

Intrapartum sonography for occiput posterior detection in early low dose combined spinal epidural analgesia by sufentanil and ropivacaine.

AIM: To evaluate the incidence of occiput posterior position in labour with and without combined spinal epidural analgesia (CSE) by low dose of sufentanyl and ropivacaine. MATERIAL AND METHODS: This study focused on 132 women subdivided in two groups, patients in spontaneous and in labour analgesia, administered by a low dose CSE by sufentanyl and ropivacaine; all women were evaluated by digital examinations and ultrasound till delivery. All data were collected and analyzed by an independent reviewer. RESULTS: In the second stage, 79 were persistent occiput posterior position (POPP) fetuses and 36 were translated from anterior to posterior position (TAPP) fetuses. Specifically, in spontaneous labour on 25 women in anterior position, there were 17 TAPP and in CSE analgesia on 28 women in anterior, there were 19 in TAPP, without significant differences. The number of asynclitisms was higher in the POPP group (84%) respect to the TAPP group (75%), so as the rate of caesarean section (67% versus 52.7%). CONCLUSIONS: The labour with low dose of ropivacaine and sufentanyl does not increase the occiput posterior position during fetal descent, leading to a POPP. Finally, since in the occiput anterior presentation labour analgesia significantly lengthens time to delivery, in the occiput posterior position this is significantly increased, with a prolonged second stage of labour and reduced time of descent of fetal head in obstetric pelvis.

[First abdominal access in gynecological laparoscopy: which method to utilize?]. / Primo accesso addominale in laparoscopia ginecologica: quale tecnica utilizzare?

The choice of the technique to enter the peritoneal cavity, during a laparoscopy, depends on a lot of variables which hinder a standardized method and, actually, it appears impossible to show, with certainty, the best method to choose for the first abdominal access in gynecological laparoscopy. The preference for one or another technique depends on the operator experience, school and speciality of the surgeon, laparoscopical upgrading and the work environment; many surgical techniques are not yet used due the limits and fears of some surgeons to change the preference in first access approaching and for the lack of operating versatility by a method or another one. A review of the scientific literature, underlines that the major problems during the first laparoscopical abdominal access are two, vascular and intestinal and their percentage is variable. In this paper we describe the large range of methods for open and closed laparoscopy and for direct access, that permit to perform a first abdominal laparoscopical access, and their major possible problems.

Alpha-interferon as induction and maintenance therapy in hairy cell leukemia: a long-term follow-up analysis.

Although in recent years the use of purine analogues has increased the percentage of long-term complete response the effect on overall survival of patients with hairy cell leukemia (HCL) is not yet clear. This study aimed to evaluate the long-term outcome (mean follow up of 92 months) of 64 patients receiving IFN as first-line therapy. IFN was well tolerated and effective. The overall response rate was 91% (PR 65%, CR 13%, GPR 13%). Forty-one patients (63%) received IFN 3 MU/ wk as maintenance therapy. The 10-yr projected survival rate of responding patients (CR and GPR 100%; PR 95%) and non-responders (SD, PD 80%) clearly shows that type of response does not affect survival. Patients receiving IFN maintenance had a statistically higher PFS than those who did not (p <0.01). This study shows that IFN is still one of the standard therapies for this disease, that achieving CR has no primary relevance for the control of the disease, and that good utilization of therapeutic resources may assure HCL patients a survival rate comparable to that of a normal, healthy population.

Heterogeneity of clonal development in chronic myeloproliferative disorders.

Recent reports have suggested a previously unexpected variability in the expression of the dominant neoplastic clone in myeloproliferative disorders (MPD). We evaluated 49 female patients with MPD and informative at the X-linked androgen receptor (AR) locus to establish the X chromosome inactivation pattern of hemopoietic cells. Whereas in chronic myelogenous leukemia (CML) the granulocytes (PMN) were uniformly of monoclonal origin, a striking heterogeneity of clonal development was found in PMN from patients with other MPD, with up to 50% of them expressing a polyclonal pattern of X inactivation.

[Thrombolytic therapy using r-TPA in Budd-Chiari syndrome in the course of myeloproliferative diseases]. / Trattamento trombolitico con r-TPA nella sindrome di Budd-Chiari in corso di malattie mieloproliferative.

Budd-Chiari syndrome is a rather unusual clinical entity; among others, myeloproliferative disorders not infrequently are reported as a cause of this syndrome. In the past prognosis of Budd-Chiari syndrome was usually very poor. However, in recent years treatment with fibrinolytic agents has proved to be often successful in Budd-Chiari syndrome, as well as in other thrombotic disorders. In particular, r-TPA has appeared to be effective, due to its thrombospecificity. Three cases of Budd-Chiari's syndrome associated with myeloproliferative disorders are described, in which r-TPA administration, together with treatment of underlying disease, resulted in a complete recanalization of sovrahepatic veins. r-TPA, due to its thrombospecificity, has been shown to be more effective than other thrombolytic agents; its use is associated with a lower number of hemorrhagic events and it may be repeated in the case of uncompleted response.

The association of cyclophosphamide and dexamethasone in advanced refractory multiple myeloma patients.

VAD is the most active regimen in refractory myeloma patients; however, the role of vincristine and doxorubicin remains unclear. Relatively high doses of cyclophosphamide (3.6 g/sqm) increased the response rate and survival in resistant MM. Cyclophosphamide and dexamethasone were administered to 28 patients with advanced refractory myeloma. Thirteen patients received cyclophosphamide 1.2 g/sqm on days 1 and 3 and dexamethasone 40 mg/day from day 1 to day 4, every 4 weeks for 6 cycles (schedule A); 15 patients were treated with cyclophosphamide 0.5 g/sqm on days 1 and 3 and dexamethasone 40 mg/day from day 1 to day 4, every two weeks for 12 cycles (schedule B). Overall, 21 patients (75%) responded and 10 achieved an objective response (36%), while 11 reached a partial response. Twenty patients died (68%), most of them of disease progression, and 8 are still alive (32%). Median length of response and survival is 6 and 8 months, respectively. Therapy was easily applied and well tolerated. The overall response rate (75%) compares favorably with the best published results in this setting. The two schedules proved to be equally effective but patients treated with schedule B had more infections, which may have been related to the higher dosage of steroids.

Multiple myeloma in the elderly: clinical features and response to treatment in 113 patients.

BACKGROUND: Considering the conflicting results of the few reports on geriatric MM patients and the increasing relevance of the problem, we analyzed a series of 113 patients over 64 years of age treated with conventional chemotherapy. PATIENTS AND METHODS: The median age was 71 (range 65-92). Stage IA, IIA, IIIA and IIIB patients numbered 28, 33, 45 and 7, respectively. The M component was IgG in 73 patients (65%), IgA in 30 (26%), IgD in 3 (3%), light chain in 5 (4%); no monoclonal component was detected in 2 (2%) cases. Sixty-three patients showed symptomatic skeletal disease. Melphalan/prednisone (MP) was the first-line treatment in 84 patients (74%). Patients were grouped according to age (> 64 < or = 74; > or = 75) in order to carry out analysis. RESULTS: Seventy-eight cases (69%) showed a sizable reduction in the tumor mass; objective and partial response was achieved in 57 (50%) and 21 (19%) patients, respectively. Patients with stage I-II disease fared significantly better than stage III patients (median survival: 70 vs 38 months; p = 0.017). Response to first-line treatment correlated with overall survival; patients with responsive or refractory disease had median survival rates of 64 and 20 months, respectively (p = 0.0001). CONCLUSIONS: Neither patients above nor below 75 years of age showed any difference in presentation features or in response to treatment. These results suggest that advanced age should not be considered a major obstacle to active treatment.

[Therapeutic aspects of hairy cell leukemia]. / Aspetti terapeutici dell'hairy cell leukemia.

This work considers the new advances in hairy cell leukemia therapy. During the last decades the only useful treatments were splenectomy, or, in case of failure or relapse, various chemotherapeutic approaches. Sometimes leukapheresis, radiotherapy, androgens, allogenic bone marrow transplantation, corticosteroids and lithium salts were used with few good results. Interferon and 2-deoxicoformycin recently introduced for the treatment of HCL have determined a dramatic change in the outlook of this disease, producing a high percentage of complete and partial remission.

[Disseminated intravascular coagulation. II. Therapeutic problems]. / La coagulazione intravascolare disseminata II. - problemi terapeutici.

The treatment of DIC often presents problems that are not easily solved given the difficulty of interpreting symptoms and haematological findings, the seriousness of the clinical situation and the rapid development of disease phenomena. Diagnostic questions must be answered before physiopathologically rational therapy can be applied. The identification and cure of the condition which triggers coagulation are also of primary importance in selecting a therapeutic response. Apart from specific treatment of the causal disease, the treatment of DIC is based on the one hand on the use of anticoagulants (heparin) to halt intravascular coagulation and transfusional integration with haemoderivatives and platelet concentrates to correct the haemostasis deficiency secondary to such massive consumption. On the other, direct methods are needed to control the state of shock, cardiorespiratory compromise and acute renal insufficiency which often complicate the course of the defibrination syndrome. Therapeutic success depends on timely intervention allied to the employment of adequate measures for each individual case.