Endoscopic management of frontal sinus diseases after frontal craniotomy: a case series and review of the literature.

PURPOSE: To evaluate frontal sinus complications developed after previous external craniotomies requiring frontal sinus reconstruction and their treatment with an endoscopic approach. METHODS: We retrospectively evaluated 22 patients who referred to Sant'Orsola-Malpighi University Hospital and Bellaria Hospital (Bologna, Italy) between 2005 and 2017. All patients presented with frontal sinus disease after frontal craniotomy with sinus reconstruction performed to treat various pathological conditions. We reported our experience in the endoscopic management of such complications and we reviewed the current literature concerning the endoscopic treatment of these conditions. RESULTS: In total, 14 frontal mucoceles, 4 cases of chronic frontal sinusitis, 2 mucopyoceles and 2 fungus ball of the frontal sinus were identified. Endoscopic surgical treatment included 7 DRAF IIa, 1 DRAF IIb, 11 DRAF III and 3 DRAF IIc (modified DRAF III) approaches. The success rate of the surgical procedure was 86% (19/22 patients). Recurrence of the initial pathology occurred in three patients (14%) requiring a conversion of previous frontal sinusotomy into a DRAF III sinusotomy. CONCLUSION: Frontal sinusopathy can be a long-term complication following craniotomies and may lead to potentially severe pathological conditions, such as mucoceles and frontal sinus inflammation. Its management is still debated and requires recovery of the patency of nasal-frontal route. Our study confirms that the endoscopic endonasal approach may offer a valid solution with low morbidity avoiding re-opening of the craniotomic access. For selected cases, endoscopic approach could also be performed simultaneously to craniotomy as a combined surgery to reduce the risk of short- and long-term complications. Long-term follow-up is mandatory in patients with a history of opened and reconstructed frontal sinus and should include imaging and endoscopic outpatient evaluation.

Sentinel node biopsy versus elective neck dissection in early-stage oral cancer: a systematic review.

PURPOSE: To provide a summary of the evidence on the comparative effectiveness of two surgical treatment strategies, sentinel node biopsy (SNB) and elective neck dissection (END), in patients with T1-T2 oral cancer and clinically negative (cN0) neck, in terms of overall survival (OS), disease-free survival (DFS) and neck recurrence rates (NRRs). METHODS: A systematic review was performed by including studies published up to April 2019. Meta-analysis was performed to compare NRRs between SNB and END. A narrative summary of the results was generated for OS, DFS and morbidity outcomes. The certainty of evidence was assessed according to the GRADE methodology. RESULTS: No randomized studies were retrieved. Five observational studies were included in the comparative effectiveness analysis and four observational studies were included in the comparative morbidity analysis. The pooled risk ratio showed no differences in NRRs between SNB and END (10.5% vs 11.6%; pooled RR 1.09; 95% CI 0.67-1.76). No differences in OS or DFS between the two treatments were found. SNB appears to be associated with a lower rate of postoperative complications and lower shoulder dysfunction than END. Conversely, the results of the quality of life (QoL) questionnaires are not sufficient to advocate a particular strategy. CONCLUSION: Our review highlights the lack of well conducted and randomized studies comparing SNB to END, leading to poor clinical evidence. Although our findings suggest no significant differences in OS, DFS and NRR between the two strategies, the certainty of our evidence is too low to make it useful for clinical decision making.

Influence of conjugation and other structural changes on the activity of Cu²âº based PNAzymes.

We have previously shown that PNA-neocuproine conjugates can act as artificial RNA restriction enzymes. In the present study we have additionally conjugated the PNA with different entities, such as oligoethers, peptides etc. and also constructed systems where the PNA is designed to clamp the target RNA forming a triplex. Some conjugations are detrimental for the activity while most are silent which means that conjugation can be done to alter physical properties without losing activity. Conjugation with a single oligoether close to the neocuproine does enhance the rate almost twofold compared to the system without the oligoether. The systems designed to clamp the RNA target by forming a triplex retain the activity if the added oligoT sequence is 5 PNA units or shorter and extends the arsenal of artificial RNA restriction enzymes. Changing the direction of a closing base pair, where the target RNA forms a bulge, from a GC to a CG pair enhances the rate of cleavage somewhat without compromising the selectivity, leading to the so far most efficient artificial nuclease reported.

Efficacy and activity of PD-1 blockade in patients with advanced esophageal squamous cell carcinoma: a systematic review and meta-analysis with focus on the value of PD-L1 combined positive score.

BACKGROUND: Recently, several randomized controlled trials (RCTs) investigated immunotherapy-based regimens versus chemotherapy alone in patients with advanced esophageal squamous cell carcinoma (ESCC). Here we conducted a systematic review and meta-analysis on the efficacy and activity of programmed cell death protein 1 blockade in these patients, with focus on the value of programmed death-ligand 1 combined positive score (CPS) for selecting patients who may benefit the most. METHODS: RCTs investigating treatment with or without immune checkpoint inhibitors for advanced ESCC were selected. The hazard ratio (HR) and the odds ratio were used to compare the treatment effect on survival outcomes and tumor response, respectively, for immunotherapy-based regimens compared with standard chemotherapy, overall and according to geographic region or treatment line. We carried out a subgroup analysis comparing patients with CPS ≥10 or <10 and the evidence for treatment effect was evaluated by interaction test. RESULTS: A total of 5257 patients and 10 RCTs were included. Overall, the HR for overall survival benefit with immunotherapy-based regimens was 0.71 [95% confidence interval (CI) 0.66-0.76] compared with chemotherapy alone; such effect was independent from geographical region (Asia versus rest of the world) and treatment line (upfront versus second/further lines). The HR for progression-free survival benefit and the odds ratio for overall response rate increase were 0.78 (95% CI 0.66-0.93) and 1.50 (95% CI 1.22-1.83), respectively. The HR for overall survival benefit with immunotherapy-based treatment was 0.60 (95% CI 0.51-0.70) for CPS ≥10 subgroup versus 0.83 (95% CI 0.69-1.00) for CPS <10 (P for interaction 0.009). CONCLUSIONS: Immune checkpoint inhibitors have a consistent benefit in reducing the risk of death for ESCC patients which is dependent on programmed death-ligand 1 CPS status. Further investigations of biomarkers for immunotherapy in the subgroup of patients with CPS <10 are needed.

Can adverse neonatal outcome be predicted in late preterm or term fetal growth restriction?

OBJECTIVE: To identify independent predictors of adverse neonatal outcome in cases of fetal growth restriction (FGR) at > or = 34 weeks. METHODS: From a cohort of 481 FGR cases delivered at > or = 34 weeks, demographic and obstetric variables, fetal biometry and Doppler indices of the uterine, umbilical and fetal middle cerebral arteries available within 2 weeks of delivery, were related to adverse neonatal outcome, defined as admission to the neonatal intensive care unit for indications other than low birth weight alone. RESULTS: Logistic regression analysis showed that gestational age (GA) at delivery (odds ratio (OR) = 0.59; 95% CI, 0.50-0.70), abdominal circumference (AC) centile (OR = 0.69; 95% CI, 0.59-0.81) and umbilical artery (UA) pulsatility index (PI) centile (OR = 1.02; 95% CI, 1.01-1.04) significantly correlated with adverse neonatal outcome. From this model we calculated a score of adverse neonatal outcome expressed by the formula: (UA-PI centile/3) - (10 x AC centile) + (10 x (40 - GA at delivery in weeks)). Receiver-operating characteristics curve analysis demonstrated that a score of > or = 25 optimally predicted adverse neonatal outcome (sensitivity of 75%, false-positive rate of 18%). Beyond 37.5 weeks, gestational age no longer had an independent impact on outcome. CONCLUSIONS: In late preterm or term FGR, GA at delivery is the most important predictor of adverse neonatal outcome. At > 37.5 weeks, delivery may be the best option to minimize adverse outcome in all FGR cases. At 34-37 weeks, a score based on GA at delivery, UA-PI centile and AC centile optimally predicts adverse neonatal outcome.

Are ultrasonographic myoma characteristics associated with blood loss at delivery?

OBJECTIVES: The presence of myomas in pregnancy is associated with greater blood loss at delivery. The aim of this study was to evaluate whether the sonographic characteristics of myomas can predict blood loss at delivery in women with large myomas. METHODS: Among women who underwent second-trimester ultrasound screening at our department between January 1996 and December 2004, 251 had at least one myoma with a mean diameter > or = 5 cm. Number of myomas (single vs. multiple), maximum diameter of the largest myoma, sum of the maximum diameter of each myoma, change in size of myomas between first and last scan, and location in relation to the placenta and to the presenting part of the fetus (above or below) were analyzed in relation to blood loss at delivery and severe postpartum hemorrhage (> or = 1000 mL). RESULTS: Multivariate analysis showed that the presence of multiple myomas was the only parameter independently associated with amount of blood loss at delivery (P = 0.003). The association between the presence of multiple myomas and severe postpartum hemorrhage was of borderline significance for the statistical power of this study (P = 0.08). CONCLUSIONS: In women with large myomas, the presence of multiple tumors is independently associated with heavier blood loss at delivery but not with postpartum hemorrhage of > or = 1000 mL.

Amnioinfusion in preterm PROM: effects on amnion and cord histology.

OBJECTIVE: To investigate the effects of transabdominal amnioinfusion (TA) on the histology of amnion (A) and umbilical cord (UC). STUDY DESIGN: From a cohort of 56 singleton pregnancies with premature rupture of membranes (PROM) at

Prenatal sonographic evaluation of male genitalia development.

AIM: The aim of this study was to evaluate the sonographic development of normal fetal male genitalia. METHODS: A longitudinal study was performed on 60 male fetuses. The development of penis, prepuce and presence of testes in scrotum were observed with a high resolution transabdominal ultrasonography between weeks 11 and 40. RESULTS: The overall success of identifying correctly the fetal male gender increased with gestational age from 46% to 80%, and 96% at 12, 13 and 14 week, respectively. The number of the scans performed in relation to the gestational age from week 11 to week 14 improves the ability to assign the male gender and to report the penile length (P<0.05); the earliest observations of descend testis were at 24 weeks. The bilateral observation of testicular descend was at 31 weeks in 98% of fetuses. CONCLUSION: Development of male genitalia is easy evaluated through the pregnancy. This could be useful to early identify male genitalia abnormalities.

Prenatal diagnosis of supernumerary ring chromosome 1: case report and review of the literature.

A supernumerary ring chromosome was found on amniocentesis performed for advanced maternal age. A review of the literature found 34 reports of supernumerary ring chromosome I which are compared to our case.

Uterine Doppler velocimetry and placental hypoxic-ischemic lesion in pregnancies with fetal intrauterine growth restriction.

We tested the hypothesis that Doppler velocimetry of the ascending uterine arteries (Ut.DV) in cases of fetal intrauterine growth restriction (IUGR) can reflect the presence of hypoxic-ischaemic lesions of the placenta, and whether this prediction is affected by the maternal blood pressure status.Ut.DV was obtained within 7 days of delivery in 90 consecutive pregnancies with IUGR and in 37 uneventful control pregnancies. Abnormal Ut.DV was defined as an average of a (left and right systolic)/diastolic ratio >2.6 and diastolic notching. After delivery, pathological studies were performed with attention paid to macroscopic and microscopic evidence of hypoxic or ischaemic placental lesions related to uteroplacental vascular pathological features. In patients with IUGR, the total rate of placental lesions was significantly higher in the presence of abnormal Ut.DV compared to the presence of normal Ut.DV (relative risk, 6.35; 95 per cent confidence interval=5.2-7.3). The rate and the severity of these lesions was not significantly different between normotensive and hypertensive pregnancies (87 versus 93 per cent;P =0.2). When Ut.DV was normal, the rate of placental lesions was similar between IUGR cases and control pregnancies (14 versus 8 per cent;P =0.69). The perinatal outcome was not significantly different in any of the normotensive and the hypertensive pregnancies with growth-restricted fetuses and abnormal Ut.DV.The presence of abnormal Doppler velocimetry of the uterine arteries in pregnancies with fetal intrauterine growth restriction is may be in fact an important indicator of hypoxic or ischaemic placental lesions. This abnormal Doppler velocimetry is independent of the maternal blood pressure status.

Risk factors for neonatal intraventricular haemorrhage in spontaneous prematurity at 32 weeks gestation or less.

In this study we aimed to establish which clinical and histopathological factors are associated with early-onset neonatal intraventricular haemorrhage (IVH) in non-iatrogenic preterm delivery before 32 weeks of gestation. We retrospectively reviewed all singleton pregnancies delivered before 32 weeks of gestation after spontaneous onset of preterm labour or preterm membrane rupture during the period January 1993 to June 1997. Clinical and histopathological data in cases with IVH diagnosed at neonatal cranial ultrasound within 72 h of birth (n = 17) were compared with those of neonates not experiencing this complication (non-IVH) (n = 54). Histological lesions analysed were those of acute inflammation and those on a uteroplacental vascular basis. Statistical methods included the Wilcoxon rank sum test, Fisher's exact test, and logistic regression analysis. A P<0.05 was considered significant.IVH and non-IVH groups were not significantly different in birthweight, gestational age at delivery, cord pH at birth, rates of 5-min Apgar score below 7, caesarean delivery, diagnosis of clinical chorioamnionitis or antenatal administration of steroids. Respiratory distress syndrome was more frequently diagnosed in the IVH than non-IVH group (64 per cent versus 33 per cent, P=0.02). Placental acute inflammatory or uteroplacental vascular lesions were present in 100 per cent of IVH neonates versus 22 per cent of non-IVH cases (P<0.001). Logistic regression analysis demonstrated that only respiratory distress syndrome (P = 0.04) and histological evidence of acute placental inflammation (P = 0.02) were significantly and independently associated with IVH. Histopathological evidence of acute inflammatory placental lesions is the best predictor of occurrence of neonatal IVH.

Antenatal corticosteroids and placental histology in preterm birth.

To assess the effects of antenatal corticosteroid use on placental histopathology, we have reviewed a database of 463 consecutive non-anomalous singleton liveborns delivered at less than 32 weeks between April 1988 and December 1994, of which 280 received one or more doses of corticosteroids for promotion of fetal lung maturation. Patients were grouped by the number of corticosteroid doses received (analyzed as none, 1, 2 and 3 or more doses). Clinical and demographic factors were recorded prospectively. Placental histopathology was reviewed blinded to clinical factors except gestational age, and 42 distinct placental lesions were examined and scored for severity. Data were analyzed by contingency tables, one-way analysis of variance, and linear regression analysis. Among clinical variables, univariate analysis showed that the number of corticosteroid doses was significantly related to presence of labour prior to delivery, pre-eclampsia, premature rupture of membranes and clinical suspicion or diagnosis of chorioamnionitis. Using linear regression analysis with these clinical variables as confounders, increased number of doses of antenatal corticosteroids was related to increased severity of villous fibrosis and stromal mineralization, and fewer villous infarcts.

Clinical correlations of patterns of placental pathology in preterm pre-eclampsia.

The objective of this study was to determine if placental histopathology patterns are associated with clinical features of preterm pre-eclampsia. A 1989-1993 database of consecutive non-anomalous singleton livebirths delivered at 22-32 weeks gestation excluding cases of maternal diabetes mellitus and chronic hypertension included 74 cases of pre-eclampsia. Placentae were scored for uteroplacental vascular lesions and lesions of chronic inflammation and coagulation. Thirteen lesion patterns identified by factor analysis were studied in relation to the clinical features. Severe maternal proteinuria was related to placental chronic inflammation, while lower maternal antepartum platelet counts were related to placental abruption and infarct. Lower birthweight percentile and lighter placentae were related directly to uteroplacental vascular lesions. Diagnosis of HELLP and coagulopathy were less common when chronic inflammation scores were high. Serologic studies related to autoimmunity and maternal blood pressures were unrelated to placental histopathology factors. It is concluded that features of maternal and fetal compromise in preterm pre-eclampsia are related to placental histopathology patterns.

Amniotic band syndrome in monozygotic twins: prenatal diagnosis and pathogenesis.

Amniotic band syndrome is a well-described disorder lacking a precise definition or a scientifically validated hypothesis of pathogenesis. The widely accepted "exogenous" theory suggests that early amniotic rupture leads to the formation of pathologic amniotic strands, which then induce nonanatomic fetal abnormalities. This paradigm appears to be challenged by observations that amniotic band syndrome occurs in monozygotic twin gestations. The exclusive development of amniotic band syndrome in monozygotic versus dizygotic twin gestations, the description of early amniotic rupture in one sac of a dizygotic twin gestation without subsequent fetal abnormalities, and the paradoxical observations of discordance in monoamniotic and concordance in diamniotic twin gestations, fail to support an "exogenous" etiology for amniotic band syndrome.

Placental vascular lesions and likelihood of diagnosis of preeclampsia.

OBJECTIVE: To test the hypothesis that a range of severity of placental vascular lesions underlies preeclampsia and that the likelihood of its clinical diagnosis increases with the extent and severity of uteroplacental vascular lesions. METHODS: Four hundred sixty-five consecutive placentas of singleton, nonanomalous, live-born infants born before 32 weeks' gestation were examined prospectively, and uteroplacental vascular and related villous lesions were assigned a semiquantitative lesion score based on severity and extent of lesions. The summed scores of individual lesions yielded a total uteroplacental vascular lesion score, ranging from 0 to 21, that was correlated with the odds of a clinical diagnosis of preeclampsia, as well as with potential confounders, including maternal age, race, gestational age at delivery, and birth weight centile. Statistical analysis was performed using contingency tables, one-way analysis of variance, multiple logistic regression, and receiver operating characteristic curve. P < .05 was considered significant. RESULTS: A clinical diagnosis of preeclampsia was present in 78 of 465 (17%) cases. Logistic regression demonstrated that the total uteroplacental vascular lesion score related significantly to the diagnosis of preeclampsia (odds ratio 1.43, 95% confidence interval 1.31, 1.57) and this association was independent of gestational age at delivery and birth weight centile. Preeclampsia was diagnosed in 12 of 284 (4%) cases with no or minimal histologic evidence of placental vascular injury (total score less than 4). Conversely, the diagnosis was not made in 4% of cases despite the presence of extensive placental vascular injury (total score at least 14). CONCLUSION: The likelihood of clinical diagnosis of preeclampsia before 32 weeks increases with progressive impairment of the uteroplacental circulation. Histopathologic examination of the placenta can be used to confirm the diagnosis of preeclampsia.

Uterine allergy: a cause of preterm birth?

OBJECTIVE: To identify the origin of eosinophils in cases of eosinophil-associated preterm delivery. METHODS: From an established set of 465 consecutive non-anomalous singleton infants delivered at 22-32 weeks' gestation, we retrieved 161 cases of preterm delivery following spontaneous onset of preterm labor, 78 cases with maternal preeclampsia, 33 cases of abruption, and 193 cases of premature rupture of membranes (PROM). Charts were reviewed, and the placenta, umbilical cord, and membranes were examined histologically. In cases with extravascular eosinophils showing evident gradient toward the amniotic cavity, the origin of the eosinophils (fetal or maternal) was determined by the proximity to fetal or maternal vessels. RESULTS: Histologic evidence of an eosinophilic gradient toward the amniotic cavity was present only in the fetal (including umbilical cord and chorion) compartments. This eosinophilic gradient was present in 19% (90 of 465) of preterm delivery cases and was significantly more common in cases of PROM (54 of 193, 28%) and preterm labor (34 of 161, 21%) than abruption (two of 33, 6%) and preeclampsia (none of 78) (P < .001). In 84 of 90 cases (93%), the eosinophilic gradient was present along with multiple histologic indicators of acute intrauterine inflammation. CONCLUSION: An eosinophilic gradient toward the amniotic cavity, present in nearly a fifth of cases of preterm delivery, is probably of fetal origin, making it unlikely that a maternal "allergy-like" mechanism is a cause of preterm delivery.

Prenatal diagnosis of duodenal atresia: does it make any difference?

The outcome of infants with duodenal atresia diagnosed antenatally is compared with that of infants diagnosed after birth. The incidence of neonatal morbidity was higher and preoperative conditions were poorer in the second group.