Delivery outcomes in the subsequent pregnancy following the conservative management of placenta accreta spectrum disorder: a systematic review and meta-analysis.

OBJECTIVE: Cesarean hysterectomy is generally presumed to decrease maternal morbidity and mortality secondary to placenta accreta spectrum disorder. Recently, uterine-sparing techniques have been introduced in conservative management of placenta accreta spectrum disorder to preserve fertility and potentially reduce surgical complications. However, despite patients often expressing the intention for future conception, few data are available regarding the subsequent pregnancy outcomes after conservative management of placenta accreta spectrum disorder. Thus, we aimed to perform a systematic review and meta-analysis to assess these outcomes. DATA SOURCES: PubMed, Scopus, and Web of Science databases were searched from inception to September 2022. STUDY ELIGIBILITY CRITERIA: We included all studies, with the exception of case studies, that reported the first subsequent pregnancy outcomes in individuals with a history of placenta accreta spectrum disorder who underwent any type of conservative management. METHODS: The R programming language with the "meta" package was used. The random-effects model and inverse variance method were used to pool the proportion of pregnancy outcomes. RESULTS: We identified 5 studies involving 1458 participants that were eligible for quantitative synthesis. The type of conservative management included placenta left in situ (n=1) and resection surgery (n=1), and was not reported in 3 studies. The rate of placenta accreta spectrum disorder recurrence in the subsequent pregnancy was 11.8% (95% confidence interval, 1.1-60.3; I2=86.4%), and 1.9% (95% confidence interval, 0.0-34.1; I2=82.4%) of participants underwent cesarean hysterectomy. Postpartum hemorrhage occurred in 10.3% (95% confidence interval, 0.3-81.4; I2=96.7%). A composite adverse maternal outcome was reported in 22.7% of participants (95% confidence interval, 0.0-99.4; I2=56.3%). CONCLUSION: Favorable pregnancy outcome is possible following successful conservation of the uterus in a placenta accreta spectrum disorder pregnancy. Approximately 1 out of 4 subsequent pregnancies following conservative management of placenta accreta spectrum disorder had considerable adverse maternal outcomes. Given such high incidence of adverse outcomes and morbidity, patient and provider preparation is vital when managing this population.

Outcomes following a clinical algorithm allowing for delayed hysterectomy in the management of severe placenta accreta spectrum.

BACKGROUND: The incidence of placenta accreta spectrum is rising. Management is most commonly with cesarean hysterectomy. These deliveries often are complicated by massive hemorrhage, urinary tract injury, and admission to the intensive care unit. Up to 60% of patients require transfusion of ≥4 units of packed red blood cells. There is also a significant risk of death of up to 7%. OBJECTIVE: The purpose of this study was to assess the outcomes of patients with antenatal diagnosis of placenta percreta that was managed with delayed hysterectomy as compared with those patients who underwent immediate cesarean hysterectomy. STUDY DESIGN: We performed a retrospective study of all patients with an antepartum diagnosis of placenta percreta at our large academic institution from January 1, 2012, to May 30, 2018. Patients were treated according to standard clinical practice that included scheduled cesarean delivery at 34-35 weeks gestation and intraoperative multidisciplinary decision-making regarding immediate vs delayed hysterectomy. In cases of delayed hysterectomy, the hysterotomy for cesarean birth used a fetal surgery technique to minimize blood loss, with a plan for hysterectomy 4-6 weeks after delivery. We collected data regarding demographics, maternal comorbidities, time to interval hysterectomy, blood loss, need for transfusion, occurrence of urinary tract injury and other maternal complications, and maternal and fetal mortality rates. Descriptive statistics were performed, and Wilcoxon rank-sum and chi-square tests were used as appropriate. RESULTS: We identified 49 patients with an antepartum diagnosis of placenta percreta who were treated at Vanderbilt University Medical Center during the specified period. Of these patients, 34 were confirmed to have severe placenta accreta spectrum, defined as increta or percreta at the time of delivery. Delayed hysterectomy was performed in 14 patients: 9 as scheduled and 5 before the scheduled date. Immediate cesarean hysterectomy was completed in 20 patients: 16 because of intraoperative assessment of resectability and 4 because of preoperative or intraoperative bleeding. The median (interquartile range) estimated blood loss at delayed hysterectomy of 750 mL (650-1450 mL) and the sum total for delivery and delayed hysterectomy of 1300 mL (70 -2150 mL) were significantly lower than the estimated blood loss at immediate hysterectomy of 3000 mL (2375-4250 mL; P<.01 and P=.037, respectively). The median (interquartile range) units of packed red blood cells that were transfused at delayed hysterectomy was 0 (0-2 units), which was significantly lower than units transfused at immediate cesarean hysterectomy (4 units [2-8.25 units]; P<.01). Nine of 20 patients (45%) required transfusion of ≥4 units of red blood cells at immediate cesarean hysterectomy, whereas only 2 of 14 patients (14.2%) required transfusion of ≥4 units of red blood cells at the time of delayed hysterectomy (P=.016). There was 1 maternal death in each group, which were incidences of 7% and 5% in the delayed and immediate hysterectomy patients, respectively. CONCLUSION: Delayed hysterectomy may represent a strategy for minimizing the degree of hemorrhage and need for massive blood transfusion in patients with an antenatal diagnosis of placenta percreta by allowing time for uterine blood flow to decrease and for the placenta to regress from surrounding structures.

Mutations in the human orthologue of the mouse underwhite gene (uw) underlie a new form of oculocutaneous albinism, OCA4.

Oculocutaneous albinism (OCA) affects approximately 1/20,000 people worldwide. All forms of OCA exhibit generalized hypopigmentation. Reduced pigmentation during eye development results in misrouting of the optic nerves, nystagmus, alternating strabismus, and reduced visual acuity. Loss of pigmentation in the skin leads to an increased risk for skin cancer. Two common forms and one infrequent form of OCA have been described. OCA1 (MIM 203100) is associated with mutations of the TYR gene encoding tyrosinase (the rate-limiting enzyme in the production of melanin pigment) and accounts for approximately 40% of OCA worldwide. OCA2 (MIM 203200), the most common form of OCA, is associated with mutations of the P gene and accounts for approximately 50% of OCA worldwide. OCA3 (MIM 203290), a rare form of OCA and also known as "rufous/red albinism," is associated with mutations in TYRP1 (encoding tyrosinase-related protein 1). Analysis of the TYR and P genes in patients with OCA suggests that other genes may be associated with OCA. We have identified the mouse underwhite gene (uw) and its human orthologue, which underlies a new form of human OCA, termed "OCA4." The encoded protein, MATP (for "membrane-associated transporter protein") is predicted to span the membrane 12 times and likely functions as a transporter.

Decreased intracellular potassium levels underlie increased progesterone synthesis during ovarian follicular atresia.

More than 99% of ovarian follicles are lost by a degenerative process known as atresia, a phenomenon characterized by apoptosis of granulosa cells. Uniquely, dying granulosa cells also greatly increase their progesterone biosynthesis while reducing estrogen production. Recent studies have documented a dramatic decrease in intracellular K+ concentration during apoptosis that plays an important role in regulating apoptotic enzymes. However, it is unclear whether this ionic change affects related processes such as the change in steroidogenesis in dying granulosa cells. To explore this question, granulosa cells were cultured in hypotonic medium, which initially swells the cells. The cells respond by extruding K+, which we have documented by fluorescence spectrophotometry. The K+ efflux osmotically draws water out the cell, returning it to a near normal volume (as measured by flow cytometry). The result is a cell of normal size with a decreased intracellular K+ concentration. FSH stimulation of these cells caused an increase in progesterone biosynthesis. This response was enhanced at higher doses of FSH, although basal progesterone production was not affected, suggesting that K+ levels may affect the gonadotropin-signaling pathway. No increase in steroidogenic acute regulatory or cholesterol side-chain cleavage cytochrome P450 mRNA was detected, although cAMP production was enhanced. These results suggest that the loss of intracellular K+ by apoptotic granulosa cells greatly facilitates FSH-stimulated progesterone production.

Interaction between water and poly(vinylpyrrolidone) containing polyethylene glycol.

Information on the interaction between water and polymers is indispensable for manufacturing solid dispersion of a drug by hot-melt extrusion because this interaction affects various properties of the water-polymer mixtures, such as their viscoelastic properties. In this study, poly(vinylpyrrolidone) K30 (PVP) containing 0%, 10%, and 20% poly(ethylene glycol) 400 (PEG) was used as model amorphous polymers. The interaction of water with these polymers was assessed by the evaluation of the glass transition temperature (Tg), the point on the isotherm corresponding to the weight of sorbed water required to form a complete monolayer on the solid surface (apparent Wm), and the maximal amount of nonfreezing water, which were measured by differential scanning calorimetry and water sorption isotherms. In all of the systems with a water content below a certain water fraction (0.1 for PVP, 0.12 for PVP-PEG 10%, and 0.16 for PVP-PEG 20%), the Tg values were successfully predicted using theoretical equations, whereas the experimental Tg values were higher than predicted for those with a water content above these water fraction levels. In addition, these values of water fraction are similar to the apparent W(m) values determined using the Guggenheim-Anderson-DeBoer (GAB) equation (0.110, 0.117, and 0.147 weight fraction of water for PVP, PVP-PEG 10%, and PVP-PEG 20%, respectively). Nonfreezing water is detected above 0.47, 0.49, and 0.51 weight fraction of water for PVP, PVP-PEG 10%, and PVP-PEG 20%, respectively. Miscibility between water and PVP or PVP-PEG seems to change according to the water content in the system. All parameters increase with the concentration of PEG in the sample. This may be explained by the fact that PEG has a larger number of polymer repeating units, which may therefore interact with water more than PVP.

Avaliação do sensor de contratilidade cardíaca em sistema DDDR - estudo multicêntrico / Cardiac contractility sensor avaluation in a DDDR system - multicentric study

Neste estudo empregou-se um sistema de estimulação DDDR, cujo indicador que controla o sensor é o estado contrátil do miocárdio. Foram 85 pacientes portadores de doença no sistema de condução cardíaca distribuídos por 15 centros de implante no Brasil. Utilizando um parâmetro do próprio controle cardíaco vascular (contratilidade cardíaca obtida pela medida da impedância intracardíaca unipolar), a adaptação da frequência cardíaca é realizada num sistema de malha fechada, possibilitando teoricamente um ajuste a todas as necessidades fisiológicas. O objetivo principal foi avaliar a resposta de freqüência do marcapasso em situações de esforço físico e mental, tanto em ambulatório (teste de esforço e estresse mental), como em atividades diárias do paciente. A programação e a calibração do sistema foram realizadas 30 dias após o implante (tempo de maturação da interface coração-eletrodo). Além das avaliações dos limiares de estimulação e sensibilidade atriais e ventriculares, foram realizados testes de estresse mental (matemático e de percepção) e teste ergométrico, monitorizados com histogramas de freqüência gravados pelo próprio marcapasso. A média dos limiares agudos de estimulação foi de 0,76Ý0,40Volts e 0,52Ý0,35Volts, de sensibilidade foi 2,59Ý1,49mV e 11,79Ý4,92mV e a da impedância foi 567Ý119 Ohms e 628Ý139 Ohms, para átrios e ventrículos, respectivamente. A média dos limiares crônicos de estimulação foi 1,34Ý0,64Volts e 1,10Ý0,57Volts e a dos de sensibilidade foi 2,82Ý1,79mV e 6,62Ý1,36mV respectivamente para átrios e ventrículos. A freqüência cardíaca variou de 5 a 160por cento nas atividades físicas e de 3 a 79por cento nas atividades mentais, com elevação apropriada logo no início da atividade. Conclui-se pela excelente performance do sensor estudado, permitindo uma adaptação de freqüência muito semelhante à do sistema nervoso autonômico de indivíduos normais

Selective antagonism of behavioural effects of nicotine by dihydro-beta-erythroidine in rats.

The influence of the nicotine antagonist dihydro-beta-erythroidine (DH beta E) was examined on various behavioural effects of nicotine in rats. Motor activity was recorded in photocell cages whereas discriminative stimulus effects were examined using two-lever drug discrimination procedures with a tandem schedule of food reinforcement (n = 8 throughout). DH beta E (0.1-3.2 mg/kg) failed to antagonise the decreases in motor activity that nicotine (0.4-0.6 mg/kg) produced in experimentally naive rats, whereas mecamylamine (1.5 mg/kg) completely blocked this effect of nicotine. DH beta E (0.1-3.2 mg/kg) antagonised the increases in motor activity that nicotine (0.4 mg/kg) produced in rats with extensive previous exposure to both nicotine and the photocell apparatus. In rats trained to discriminate either 0.1 or 0.4 mg/kg nicotine from saline, DH beta E (0.1-3.2 mg/kg) blocked the discriminative stimulus effect of nicotine. The block of the discriminative effect could be reversed by increasing the dose of nicotine; DH beta E (1.6 mg/kg) shifted the dose-response curve for nicotine discrimination to the right by a factor of 9.4. In addition, nicotine in doses of 0.32-0.64 mg/kg decreased the overall rate of lever pressing but DH beta E (1.6 mg/kg) did not influence the dose-response curve for this effect. Thus, DH beta E potently blocked the locomotor activating and discriminative stimulus effects of nicotine at doses that did not antagonise its locomotor depressant and operant response rate-reducing effects. This selective blockade supports the involvement of different subtypes of nicotinic receptor in the mediation of diverse behavioural effects. Furthermore, the rightward shift of the dose-response curve for nicotine discrimination suggested a competitive mode of action for DH beta E.

The amphibian melanization inhibiting factor (MIF) blocks the alpha-MSH effect on mouse malignant melanocytes.

We have found that a melanization inhibitory factor (MIF) extracted from the ventral skin of Rana forreri has a slight inhibitory effect on the activity levels of tyrosinase and dopachrome tautomerase in B16/F10 and Cloudman S-91 murine melanoma cell lines. Furthermore, this factor appears to block the effects of alpha-MSH on these enzymatic activities. However, MIF treatment does not affect the melanogenic action of theophylline on the same cells, suggesting that MIF acts proximal to MSH-mediated cAMP formation, possibly by interaction with the MSH receptor. In this way, we show that this amphibian factor has biological activity on mammalian melanocytes. This suggests the existence of mammalian counterparts of amphibian MIF in the mouse integument that might regulate epidermal melanocytes. These peptides might be related to the agouti protein, as they share similar mechanisms of action. The interaction of different peptides with the MSH receptor would be a complex but general mechanism responsible for many mammalian coat color variants.

Isolation and characterization of a mouse homolog of the X-linked ocular albinism (OA1) gene.

Ocular albinism type 1 (OA1) is an X-linked human genetic disorder that affects retinal pigment cells and, to a lesser degree, neural crest-derived melanocytes. The OA1 gene is located close to the pseudoautosomal region and predicts a novel protein whose function is unknown. However, histologic studies of affected patients have suggested a potential role in melanosome biogenesis. Here we report the isolation and characterization of the mouse homolog of the human OA1 gene, termed Moa1. Two Moa1 isoforms were isolated from a melanoma cDNA library and predicted to encode proteins of 405 and 249 amino acids with six and two transmembrane-spanning regions, respectively. Interspecific backcross mapping yielded a map order and distances (cM) of cen-Moa1-3.1 +/- 1.8-Piga-2.1 +/- 1.5-Amel, indicating that Moa1 is located much farther away from the pseudoautosomal region than its human homolog. In adult tissues, both Moa1 isoforms were detected in the eye by Northern hybridization. In neonatal tissues, Moa1 RNA was detected in both skin and eyes by Northern hybridization and was not affected by the absence of pigment in mice carrying the albino mutation, or by the type of pigment synthesized, i.e., eumelanin vs pheomelanin, in mice carrying the black-and-tan mutation. Expression of Moa1 RNA was not detected in embryonic tissues by Northern analysis or by in situ hybridization despite the active synthesis of ocular pigment by E16.5. These results provide insight into the structure and possible function of the OA1 protein and suggest a more complex relationship between the human and mouse X chromosomes than was previously thought to exist.

Separation and determination of diesel contaminants in various fish products by capillary gas chromatography.

A semiquantitative capillary column gas chromatographic method is described for the determination of diesel fuel contamination in various canned seafood products. The diesel contaminants are separated from the fish sample by steam distillation, with little carry-over of interfering intrinsic materials such as fish oils. The diesel fuel is extracted from the condensate with n-hexane, and the extract is analyzed on an SPB-1 fused silica capillary column. The efficiency of recovery of diesel fuel added to canned seafood at levels of 40-400 ppt ranged from 72 to 102%. With the additional step of concentrating the hexane extract, the sensitivity of this procedure may be increased at least 10-fold. This procedure can detect the differences among diesel fuel grades No. 1, 2, and 5, and variations within diesel grade No. 2, and thus may be useful in determining the type of petroleum contaminants present in various canned fish products.

Pregnancy diagnosis in dairy herds in England and Wales.

A survey of 1692 dairy farmers in England and Wales in 1979 revealed that 14.2 per cent had veterinary pregnancy diagnoses carried out on more than half their cows, 43.8 per cent on less than half and 42.0 per cent had none. The results showed a considerable increase in the use of pregnancy diagnosis since a survey in 1969. Farmers with larger herds tended to make more use of pregnancy diagnosis and there were also some regional differences. In 64.6 per cent of herds pregnancy diagnosis was carried out during the third and fourth months of pregnancy; 93.3 per cent of herds in which more than half the cows were diagnosed were examined before the fourth month. Owners of pedigree herds used pregnancy diagnosis more than commercial herd owners. The milk progesterone assay pregnancy test was used by 4.3 per cent of farmers on more than half their cows, and by a further 1.9 per cent of farmers on some cows. More than 75 per cent of farmers using the milk progesterone test also used veterinary pregnancy diagnosis in their herds.

Gas-liquid chromatographic determination of nikethamide in injectable preparations.

A gas-liquid chromatographic (GLC) method, using a 4% XE-60 on 80-100 mesh Gas-Chrom Q column, a flame ionization detector, and anthracene as the internal standard, has been developed for the direct determination of nikethamide. Eight collaborators analyzed 4 samples, using methanol as the solvent; the coefficients of variation obtained ranged from 1.19 to 3.20%. In a limited study with acetone as the solvent, the coefficients of variation ranged from 0.59 to 1.96%. The GLC method with acetone as a solvent has been adopted as official first action.