Prenatal prediction of adverse outcome using different charts and definitions of fetal growth restriction.

OBJECTIVE: Antenatal growth assessment using ultrasound aims to identify small fetuses that are at higher risk of perinatal morbidity and mortality. This study explored whether the association between suboptimal fetal growth and adverse perinatal outcome varies with different definitions of fetal growth restriction (FGR) and different weight charts/standards. METHODS: This was a retrospective cohort study of 17 261 singleton non-anomalous pregnancies at ≥ 24 + 0 weeks' gestation that underwent routine ultrasound at a tertiary referral hospital. Estimated fetal weight (EFW) and Doppler indices were converted into percentiles using a reference standard (INTERGROWTH-21st (IG-21)) and various reference charts (Hadlock, Fetal Medicine Foundation (FMF) and Swedish). Test characteristics were assessed using the consensus definition, Society for Maternal-Fetal Medicine (SMFM) definition and Swedish criteria for FGR. Adverse perinatal outcome was defined as perinatal death, admission to the neonatal intensive care unit at term, 5-min Apgar score < 7 and therapeutic cooling for neonatal encephalopathy. The association between FGR according to each definition and adverse perinatal outcome was compared. Multivariate logistic regression analysis was used to test the strength of association between ultrasound parameters and adverse perinatal outcome. Ultrasound parameters were also tested for correlation. RESULTS: IG-21, Hadlock and FMF fetal size references classified as growth-restricted 1.5%, 3.6% and 4.6% of fetuses, respectively, using the consensus definition and 2.9%, 8.8% and 10.6% of fetuses, respectively, using the SMFM definition. The sensitivity of the definition/chart combinations for adverse perinatal outcome varied from 4.4% (consensus definition with IG-21 charts) to 13.2% (SMFM definition with FMF charts). Specificity varied from 89.4% (SMFM definition with FMF charts) to 98.6% (consensus definition with IG-21 charts). The consensus definition and Swedish criteria showed the highest specificity, positive predictive value and positive likelihood ratio in detecting adverse outcome, irrespective of the reference chart/standard used. Conversely, the SMFM definition had the highest sensitivity across all investigated growth charts. Low EFW, abnormal mean uterine artery pulsatility index (UtA-PI) and abnormal cerebroplacental ratio were significantly associated with adverse perinatal outcome and there was a positive correlation between the covariates. Multivariate logistic regression showed that UtA-PI > 95th percentile and EFW < 5th percentile were the only parameters consistently associated with adverse outcome, irrespective of the definitions or fetal growth chart/standard used. CONCLUSIONS: The apparent prevalence of FGR varies according to the definition and fetal size reference chart/standard used. Irrespective of the method of classification, the sensitivity for the identification of adverse perinatal outcome remains low. EFW, UtA-PI and fetal Doppler parameters are significant predictors of adverse perinatal outcome. As these indices are correlated with one other, a prediction algorithm is advocated to overcome the limitations of using these parameters in isolation. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Efficacy and tolerability of injectable collagen-containing products in comparison to trimecaine in patients with acute lumbar spine pain (Study FUTURE-MD-Back Pain).

Low back pain (LBP) represents an important subgroup of vertebrogenic pain with estimated prevalence around 80 %. Locally acting injectable collagen for topical application has recently extended the limited range of treatment options. The aim of the study was to evaluate the efficacy and safety of injectable collagen in patients with LBP. Patients suffering from LBP (< three months) were enrolled. They were administered either collagen 4 ml or trimecaine 1 % 4 ml in the form of subcutaneous paravertebral injections into eight pre-specified points (0.5 ml per each point) in the following schedule: two administrations in the first and second week, one in the third week. The pain intensity, Thomayer distance, Oswestry disability index, Lasseque test, quality of life, consumption of rescue medication and safety were evaluated. Exertional and rest pain, evaluated by a visual analogue scale, gradually decreased in both groups. Both treatments showed a statistically significant improvement in mobility and quality of life. The consumption of paracetamol as a rescue medication was significantly lower in patients treated with collagen than in the group treated with trimecaine (p=0.048). The analgesic efficacy of locally acting injectable collagen, as well as an analgesic sparing effect when compared to local anesthetics were demonstrated.

Chronic Low Back Pain: Current Pharmacotherapeutic Therapies and a New Biological Approach.

Chronic low back pain (CLBP) syndrome represents one of the leading causes of long-term disability worldwide. The prevalence of CLBP has been rising significantly in relation to increasing average life expectancy. CLBP results from chronification of acute low back pain. There are many factors contributing to the CLBP crisis; common etiopathogenetic factors include e.g., functional blockage of intervertebral joints. The treatment of CLBP is complex. An important part of treatment consists of pain pharmacotherapy, for which several groups of drugs are used. The problem lies in the side effects of many of these traditionally used medications. Therefore, new and safer treatment methods are being sought. Innovative options for CLBP pharmacology include injections containing collagen, which can be combined with other traditionally used drugs, which helps reduce dosages and increase the overall safety of CLBP therapy.

Electroclinical, MRI and neuropathological study of 10 patients with nodular heterotopia, with surgical outcomes.

We present the results of a retrospective study on 10 patients operated on for intractable epilepsy associated with nodular heterotopia as identified by high resolution MRI. Seven patients had unilateral heterotopia, one patient had symmetric bilateral heterotopia and two patients had asymmetric bilateral heterotopia. By stereo-electroencephalogram (SEEG) (nine patients) interictal activity within nodules was similar in all cases, and ictal activity never started from nodules alone but from the overlying cortex or simultaneously in nodules and cortex. Excellent outcomes (Engel class Ia, 1987) were achieved in the seven patients with unilateral heterotopia, showing that surgery can be highly beneficial in such cases when the epileptogenic zone is carefully located prior to surgery by MRI and particularly SEEG. For the bilateral cases surgical outcomes were Engel IIa (one patient) or Engel IIIa (two patients). Histological/immunohistochemical studies of resected specimens showed that all nodules had similar microscopic organization, even though their extent and location varied markedly. The overlying cortex was dysplastic in nine patients, but of normal thickness. We suggest that nodule formation may be the result of a dual mechanism: (i) failure of a stop signal in the germinal periventricular region leading to cell overproduction; and (ii) early transformation of radial glial cells into astrocytes resulting in defective neuronal migration. The intrinsic interictal epileptiform activity of nodules may be due to an impaired intranodular GABAergic system.

Chondroitin sulfate proteoglycans in the rat thalamus: expression during postnatal development and correlation with calcium-binding proteins in adults.

Postnatal expression of chondroitin sulfate proteoglycans was studied in the rat thalamus by immunocytochemistry and Western immunoblotting techniques with monoclonal antibodies that recognize carbohydrate epitopes (clones CS-56, 1-B-5, 2-B-6). The complex of the results shows that these antibodies recognize mostly nonoverlapping molecules whose expression is regulated during postnatal development. Chondroitin sulfate proteoglycans, recognized by antibody CS-56, and hyaluronan, identified by antibody 1-B-5 after hyaluronidase digestion, are abundant in the neuropil of most thalamic nuclei at the perinatal stage and progressively decrease during the second week of life, attaining levels barely detectable by immunocytochemistry at the end of the third week. In adult thalamus, chondroitin sulfate proteoglycans of high molecular mass, bearing glycosaminoglycans unsulfated in the linking region, and recognized by antibody 1-B-5 are confined to perineuronal nets around neurons chiefly localized in thalamic reticular nucleus. The immunoreactvity for antibody 2-B-6, specific for chondroitin-4-sulfate, is low at the perinatal stage and is not detectable in adult thalamus. Double-immunolabeling has shown that, along the rostrocaudal extension of reticular nucleus, the most developed perineuronal nets are associated with a subset of neurons expressing calretinin, and not with parvalbumin-positive neurons, which represent the largest neuronal population of the nucleus. The distribution of perineuronal nets supports the presence, in thalamic reticular nucleus, of neuronal subpopulations with different morphological and physiological features.

Pulmonary resection for lung cancer in HIV-positive patients with low (<200 lymphocytes/mm(3)) CD4(+) count.

The clinical improvement obtained with combination treatment has modified the therapeutic approach of lung cancer in HIV-positive patients. Aggressive surgical treatment has become a viable option for those patients in whom the CD4(+) cell count was greater than 200 lymphocytes/mm(3). We recently extended our surgical indications to include two HIV-positive patients with lung cancer (stage IIIA and IIB) and low (<200 lymphocytes/mm(3)) CD4(+) count. Both patients underwent a lobectomy and mediastinal nodal dissection. The postoperative course was uneventful. No evidence of recurrent cancer was seen at 12 and 20 months after the operation. Based on this limited experience, we conclude that a low CD4(+) count should not represent, per se, an exclusion criterion for the surgical treatment of pleuropulmonary conditions in HIV-positive patients.

Prognostic factors after surgical treatment of lung cancer invading the diaphragm.

BACKGROUND: Diaphragmatic invasion from lung cancer (T3-diaphragm) is a rare occurrence reported to portend a poor prognosis. METHODS: Fifteen patients with T3-diaphragm (14 males, 1 female; median age, 64 years) were surgically treated over a twenty-year period by en bloc resection (14 patients). One patient was only explored. Pathologic stage IIB (T3N0) was found in 11 patients. A partial infiltration of the diaphragm was observed in 3 patients, whereas full-depth invasion was found in 12. Diaphragmatic reconstruction was done primarily in 9 patients, and, by prosthetic material in 5. RESULTS: Two patients are still alive without evidence of disease at 88, and, 114 months from surgery. Overall median survival was 23 months (range, 3 to 168). The actuarial 5-year survival was 20%, when all patients were considered, and, 27%, for T3N0 patients. Univariate analysis showed that prosthetic replacement of the muscle (p = 0.018) was significantly related to survival. CONCLUSIONS: T3-diaphragm is best treated with en bloc resections with wide tumor-free margins and prosthetic replacement of the diaphragm.

Hepatocellular carcinoma: comparison between liver transplantation, resective surgery, ethanol injection, and chemoembolization.

Between January 1989 and June 1997, 533 patients (423 male, 110 female, mean age 61 years, range 22-89 years) with hepatocellular carcinoma (HCC) were observed at our center. We report on 419 patients retrospectively compared for different treatments: liver transplantation (LT; 55 patients), resective surgery (RS; 41 patients), transarterial chemoembolization (TACE; 171 patients) and percutaneous ethanol injection (PEI; 152 patients). The 3- and 5-year actuarial survival rates were, respectively, 72% and 68% for LT, 64 and 44% for RS, 54 and 36% for PEI, and 32 and 22% for TACE. Survival curves were compared for sex, age, tumor characteristics, alphafetoprotein level, Child class, and etiology of cirrhosis. All patient-related characteristics examined (sex, age) are not significantly related to patient survival. Tumor-related variables and associated liver disease variables significantly conditioned survival in relation to different treatments. LT seems to be the treatment of choice for monofocal HCC less then 5 cm in diameter and in selected cases of plurifocal HCC.

Left thoracic approach for cancer of cardia: early and late results.

BACKGROUND: The surgical treatment of cancer of the cardia is controversial and results are often disappointing. Concern exists not only with regards to the surgical approach but also to the extent of the resection. The authors analyze their experience over a 20-year period adopting almost exclusively a "limited" esophagogastrectomy with a wide regional lymphadenectomy through a left thoracotomy. The aim of the study is to determine if this approach actually plays a role in the treatment of this tumor. METHODS: 148 patients were evaluated for cardial cancer. Of these 22 (14.8%) were not resectable and 6 (4%) received other types of resections for technical reasons. 120 patients are the basis of the present analysis. More than 75% of patients were in stage III or IV. Follow-up was completed in 92.5% of cases; all surviving patients had at least 5 years of follow-up. RESULTS: Four (3.3%) patients died in the postoperative period. In 6 cases (5%) an anastomotic leakage occurred and this caused the death of 2 patients. Nine (7.5%) patients had severe pulmonary complications. Dysphagia was relieved in all non complicated patients. 13 (10.8%) patients had anastomotic recurrence. Overall survival rate after 5 years was 25.62 +/- 6.1%. A significant difference in survival was noted in patients at stages II and III after 5 years (61.3% vs 18.6, p < 0.02). CONCLUSIONS: This operation has proved to be a good option providing satisfying long-term results and a lower incidence of complications if compared with more extended procedures. It can be performed in the majority of patients with carcinoma of the cardia with a low mortality and morbidity and with excellent palliation of dysphagia. In our opinion it remains an optimum treatment for cardial cancer.

Ultrastructural characterization of the postnatal development of the thalamic ventrobasal and reticular nuclei in the rat.

Electron microscopy has been employed to analyze the normal maturational sequence that characterizes the postnatal development of synaptic circuits in the ventrobasal (VB) and reticular (Rt) thalamic nuclei of rats at different ages (from birth to the end of the third postnatal week). Throughout the first postnatal week, similar signs of immaturity are observed in both nuclei, mainly consisting in scarcity of cytoplasmic organelles, presence of wide extracellular spaces, and absence of myelinated fibers. Several synaptic terminals are however present from birth, thus indicating that some of the afferents have already reached and contacted their thalamic target during embryonic life. Most of the terminals are small and contain only a few round, clear vesicles, and therefore their cytological features do not allow the identification of their origin. In particular, in both nuclei, terminals with flat vesicles and symmetric specialization are only rarely observed, and in VB the ascending terminals are not distinguishable from terminals of other sources as they are in adults. During the second postnatal week, progressive maturational changes in VB and Rt lead to neurons having well-developed cytoplasmic organelles and to an elaborate neuropil containing myelinated fibers and synaptic terminals that are morphologically heterogeneous and resemble the adult ones. The permanence of growth cone-like profiles and of numerous somatic and dendritic protrusions, often contacted by synaptic terminals, indicates that a certain degree of reorganization is still taking place in both nuclei. By the end of the third postnatal week the synaptic organization of VB and Rt is indistinguishable from that observed in adults. This ultrastructural study shows that the appearance of the neuropil of VB and Rt and the morphological complexity of the synaptic arrangements characteristic of the adult rat are not present in neonates, but are gradually acquired during the first three postnatal weeks, and that they result from progressive modifications in circuit organization involving both pre- and postsynaptic elements.

Biliary complications in orthotopic liver transplantation: experience with a modified technique of duct-to-duct reconstruction.

Biliary complications are described as frequent causes of morbidity during the postoperative course of orthotopic liver transplantation (OLTx), even in recent papers. The authors report here on their experience with duct-to-duct anastomosis as their method of choice for biliary reconstruction in a consecutive series of 100 OLTx in adult patients. The original technique, as described by Starzl, was modified by the authors by performing a wide, longitudinal plasty of both the donor and recipient bile ducts, joined together with two polidioxanone running sutures, producing the effect of a side-to-side anastomosis. This technique was used in all procedures, even when a significant discrepancy was evident between the ducts (n = 10). Follow-up was completed in 100% of the patients for a period of 2-40 months (mean 13.1 months). Four major complications (4%) occurred including hepatic abscesses due to ascending cholangitis, T-tube dislocation, partial occlusion by a branch of the T-tube at the anastomotic site, and disruption of the bile duct after T-tube removal. In four other patients, transient abdominal pain followed removal of the stent. Neither strictures nor fistulas were observed. Choledochocholedochostomy on a T-tube stent represents, in our experience, the technique of choice for biliary reconstruction in OLTx. The procedure, as described in the present study, proved to be safe in preventing strictures and leakages and appears to be feasible in nearly 100% of all adult patients undergoing OLTx.

Thromboendarterectomy (TEA) in the recipient as a major risk of arterial complication after kidney transplantation.

The authors analyze a series of 383 kidney transplantation pointing out the role of recipient's vessels atherosclerosis in the determination of vascular complication of the kidney graft. Three groups were considered. The first included 55 patients which required TEA for severe atherosclerotic lesion of the anastomosed vessels. The second group included 305 patients who didn't required TEA; the third group was of 20 patients who received a graft with multiple arteries which required more than one anastomosis. A significative higher rate of arterial complications was evident in the first group (p less than 0.001). Within this group the end to end arterial anastomosis was more frequently associated to thrombosis or stenosis than the end to side one (p less than 0.05). Kidney with multiple vessels also presented with an higher rate of complications (p less than 0.05).