Hippocampal Theta Oscillations Support Successful Associative Memory Formation

Models of memory formation posit that episodic memory formation depends critically on the hippocampus, which binds features of an event to its context. For this reason, the contrast between study items that are later recollected with their associative pair versus those for which no association is made fails should reveal electrophysiological patterns in the hippocampus selectively involved in associative memory encoding. Extensive data from studies in rodents support a model in which theta oscillations fulfill this role, but results in humans have not been as clear. Here, we used an associative recognition memory procedure to identify hippocampal correlates of successful associative memory encoding and retrieval in patients (10 females and 9 males) undergoing intracranial EEG monitoring. We identified a dissociation between 2–5 Hz and 5–9 Hz theta oscillations, by which power increases in 2–5 Hz oscillations were uniquely linked with successful associative memory in both the anterior and posterior hippocampus. These oscillations exhibited a significant phase reset that also predicted successful associative encoding and distinguished recollected from nonrecollected items at retrieval, as well as contributing to relatively greater reinstatement of encoding-related patterns for recollected versus nonrecollected items. Our results provide direct electrophysiological evidence that 2–5 Hz hippocampal theta oscillations preferentially support the formation of associative memories, although we also observed memory-related effects in the 5–9 Hz frequency range using measures such as phase reset and reinstatement of oscillatory activity.SIGNIFICANCE STATEMENT Models of episodic memory encoding predict that theta oscillations support the formation of interitem associations. We used an associative recognition task designed to elicit strong hippocampal activation to test this prediction in human neurosurgical patients implanted with intracranial electrodes. The findings suggest that 2–5 Hz theta oscillatory power and phase reset in the hippocampus are selectively associated with associative memory judgments. Furthermore, reinstatement of oscillatory patterns in the hippocampus was stronger for successful recollection. Collectively, the findings support a role for hippocampal theta oscillations in human associative memory.     

Uterine Vascular Lesions

Vascular lesions of the uterus are rare; most reported in the literature are arteriovenous malformations (AVMs). Uterine AVMs can be congenital or acquired. In recent years, there has been an increasing number of reports of acquired vascular lesions of the uterus following pregnancy, abortion, cesarean delivery, and curettage. It can be seen from these reports that there is confusion concerning the terminology of uterine vascular lesions. There is also a lack of diagnostic criteria and management guidelines, which has led to an increased number of unnecessary invasive procedures (eg, angiography, uterine artery embolization, hysterectomy for abnormal vaginal bleeding). This article familiarizes readers with various vascular lesions of the uterus and their management.Key words: Uterine arteriovenous malformations, Uterine hemangioma, Placental chorioangioma, Uterine arteriovenous fistula, Uterine pseudoaneurysm, Acquired AVMVascular lesions of the uterus are very rare; most reported in the literature are arteriovenous malformations (AVMs). Uterine vascular malformations can be congenital or acquired. Recently, there has been a rise in the number of reported cases following pregnancy, abortion, and curettage. Many of these studies report spontaneous resolution of vascular lesions during follow-up; in addition, there is an increasing trend toward use of uterine artery embolization (UAE) to treat these lesions. In many of the reported studies, the diagnosis of uterine vascular malformation was made as early as the second day after a delivery or an abortion. In a study by Timmerman and colleagues,¹ out of 30 cases reported as uterine AVM based on Doppler study, only 3 were true AVMs. Rufener and associates² conducted a sonologic evaluation of postpartum and postabortion uterine vascular lesions that were reported as AVMs; the study revealed that, on pathologic examination, none turned out to be AVMs. Thus, we observe that there is confusion with regard to the terminology of vascular lesions such as uterine AVM, vascular malformation, arteriovenous fistula (AVF), and non-AVM vascular abnormalities of the uterus. The term malformation, however, is generally used to describe defects in the structure of an organ or region of the body resulting from an intrinsically abnormal process of development. Therefore, spontaneous resolution of a malformation in a short period of time is unlikely. An investigation by Mulliken and Glowacki,³ published in 1982, provided the groundwork for a proper identification of vascular lesions. Vascular tumors grow by cellular (mainly endothelial) hyperplasia: the very common hemangioma is, in reality, a benign vascular tumor. In contrast, vascular malformations have a quiescent endothelium and are considered to be localized defects of vascular morphogenesis, likely caused by dysfunction in pathways regulating embryogenesis and vasculogenesis. Therefore, the terms vascular abnormality or vascular lesion seem to best describe hypervascular areas within the uterus seen on color Doppler ultrasound, unless they are proven to be an AVM by angiography or pathologic examination. Many of these vascular lesions are increasingly being managed by UAE. Although there have been various reports of successful pregnancy following UAE, there have also been reports of ectopic pregnancy following UAE.⁴It is important to correctly identify various vascular lesions in the uterus to avoid unnecessary invasive intervention. This article aims to familiarize the reader with various vascular lesions of the uterus and their management.Uterine AVM is a rare condition, and the true incidence is not yet known. A study by O’Brien and associates⁵ showed an incidence of AVM of 4.5% in 464 pelvic sonographic examinations performed for pelvic bleeding. AVM has been described in patients between 18 and 72 years of age, and may be congenital or acquired pathologic conditions.⁶ The congenital form is very rare and is the result of a defect in embryonic vascular differentiation or a premature arrest in the development of the capillary plexus leading to multiple abnormal connections between arteries and veins.⁷ These congenital AVMs often penetrate the surrounding tissue and can cause an elaborate collateral vascular network. Furthermore, these congenital lesions can grow as pregnancy progresses.⁸The International Society for the Study of Vascular Anomalies classification system divides vascular anomalies into two primary biologic categories: (1) vasoproliferative or vascular neoplasms and (2) vascular malformations. The major distinction between the two categories is whether there is increased endothelial cell turnover, which is ultimately determined by the identification of mitoses seen on histopathology. Vasoproliferative neoplasms have increased endothelial cell turnover (ie, they proliferate and undergo mitosis) because they are neoplasms. Vascular malformations do not have increased endothelial cell turnover; rather, they are structural abnormalities of the capillary, venous, lymphatic, and arterial system, and can be congenital or acquired.     

Photodermatoses in India

Photodermatoses are a group of disorders resulting from abnormal cutaneous reactions to solar radiation. They include idiopathic photosensitive disorders, drug or chemical induced photosensitivity reactions, DNA repair-deficiency photodermatoses and photoaggravated dermatoses. The pathophysiology differs in these disorders but photoprotection is the most integral part of their management. Photoprotection includes wearing photoprotective clothing, applying broad spectrum sunscreens and avoiding photosensitizing drugs and chemicals.     

Need for urodynamic evaluation as a regular follow-up tool in assessment of long-term urological outcomes in patients with sacrococcygeal teratoma

AimTo assess the long-term urologic outcomes in follow-up of patients of sacrococcygeal teratoma (SCT) using urodynamic study (UDS) in addition to clinical and radiologic evaluation.MethodsA prospective study of clinical, radiological and urodynamic evaluation in patients with SCT who underwent resection between January 2002–June 2015 and were followed up till January 2016 was conducted.ResultsTotal 57 patients, 42 (73.7%) females and 15 (26.3%) males with 35 (62.4%) following treatment for benign and 22 (38.5%) for malignant disease were included. Twenty-eight of 57 (49.12%) had urological problems. Clinical complaints in 21 (36.8%) patients included stress urinary incontinence-14 (66.7%), enuresis-9 (42.9%), and poor stream or dribbling of urine-6 (28.6%). Eight of 51 patients (15.7%) had abnormal ultrasound findings, which included contracted, trabeculated thick walled bladder (3), bilateral hydronephrosis (3) and significant post void residue (PVR) (6). Seven of 57 underwent micturating cystourethrogram (MCU), 5 had an abnormal report[significant PVR (4), small trabeculated bladder (3), reflux (2) and large capacity bladder (1)]. Urodynamic study was done in 27 patients, 18/27 (66.7%) had abnormalities. Six patients without any clinical or ultrasonographic abnormalities had abnormal UDS. Total 28 (49.12%) had urological comorbidities. Three patients had overactive bladder, five dysfunctional voiding, one underactive bladder and one had giggle incontinence. Children were managed by behaviour therapy and pharmacotherapy.ConclusionUrodynamic evaluation could detect abnormalities in patients who had no urinary complaints or abnormality on ultrasound. The abnormalities have a potential for progressive upper tract damage. Urodynamics should be an integral part of urological surveillance in patients operated for SCT.Type of studyPrognostic study.Level of EvidenceLevel II (Prospective cohort study).     

Efficacy of Second-line Targeted Therapy for Renal Cell Carcinoma According to Change from Baseline in International Metastatic Renal Cell Carcinoma Database Consortium Prognostic Category

Background

We hypothesized that changes in International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) prognostic category at start of second-line therapy (2L) for metastatic renal cell carcinoma (mRCC) might predict response.

Cytoreductive Nephrectomy in Patients with Synchronous Metastases from Renal Cell Carcinoma: Results from the International Metastatic Renal Cell Carcinoma Database Consortium

Background

The benefit of cytoreductive nephrectomy (CN) for overall survival (OS) is unclear in patients with synchronous metastatic renal cell carcinoma (mRCC) in the era of targeted therapy.

Objective

To determine OS benefit of CN compared with no CN in mRCC patients treated with targeted therapies.

Design, setting, and participants

Retrospective data from patients with synchronous mRCC (n = 1658) from the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) were used to compare 982 mRCC patients who had a CN with 676 mRCC patients who did not.

Outcome measurements and statistical analysis

OS was compared and hazard ratios (HRs) adjusted for IMDC poor prognostic criteria.

Results and limitations

Patients who had CN had better IMDC prognostic profiles versus those without (favorable, intermediate, or poor in 9%, 63%, and 28% vs 1%, 45%, and 54%, respectively). The median OS of patients with CN versus without CN was 20.6 versus 9.5 mo (p < 0.0001). When adjusted for IMDC criteria to correct for imbalances, the HR of death was 0.60 (95% confidence interval, 0.52–0.69; p < 0.0001). Patients estimated to survive <12 mo may receive marginal benefit from CN. Patients who have four or more of the IMDC prognostic criteria did not benefit from CN. Data were collected retrospectively.

Conclusions

CN is beneficial in synchronous mRCC patients treated with targeted therapy, even after adjusting for prognostic factors. Patients with estimated survival times <12 mo or four or more IMDC prognostic factors may not benefit from CN. This information may aid in patient selection as we await results from randomized controlled trials.

Patient summary

We looked at the survival outcomes of metastatic renal cell carcinoma patients who did or did not have the primary tumor removed. We found that most patients benefited from tumor removal, except for those with four or more IMDC risk factors.     

Pediatric snow sport injuries differ by age

BackgroundUnintentional injury is the leading cause of death among pediatric patients. There were 13,436 injuries related to snow sports in those younger than 15 in 2015, with 4.8% requiring admission. These sports are high-risk given the potential for injury even when using protective equipment. We hypothesized that snow sport injury patterns would differ based on patient age.MethodsA cross-sectional analysis of the 2009 and 2012 Kids' Inpatient Database was performed.Cases of injuries were identified and analyzed using ICD-9 codes. National estimates were obtained using case weighting. Multivariable logistic regression was used to assess for confounders.ResultsWithin 745 admissions, there was a statistically significant decrease in skull/facial fractures with increasing age and a statistically significant increase in abdominal injuries with increasing age. Children in early and middle childhood were at increased odds of being hospitalized with skull/facial fractures, while older children were more likely hospitalized with abdominal injuries.ConclusionsWithin the pediatric snow sport population, younger children are more likely to experience head injuries, while older children are more likely to experience abdominal injuries.Further research is needed to determine the origin of this difference, and continued legislation on helmets is also necessary in reducing intracranial injuries.Level of EvidenceIII     

Simultaneous combined liver and kidney transplantation: a single center experience

Chava SP, Singh B, Stangou A, Battula N, Bowles M, O’Grady J, Rela M, Heaton ND. Simultaneous combined liver and kidney transplantation: a single center experience.
Clin Transplant 2010: 24: E62–E68. © 2010 John Wiley & Sons A/S. Abstract Renal dysfunction is common in patients awaiting liver transplantation (LT) and affects outcome following LT. Combined liver and kidney transplantation (CLKT) has been proposed as effective treatment for patients with chronic diseases of both organs, some with hepatorenal syndrome and for liver‐based metabolic diseases affecting kidney. This study is undertaken to analyze results of CLKT at a single center. Of 2690 LTs performed between 1992 and 2007, there were 39 CLKTs; most common indications were metabolic, cirrhosis and polycystic disease. With follow‐up of up to 170 months, 11 died (overall survival 71.8%); one‐, five‐, and 10‐yr patient and liver graft survival is 77%, 73.7%, and 73.7%, respectively, and kidney graft survival is 77%, 70%, and 70%, respectively. Survival among metabolic group (78.6%) appeared to be better than non‐metabolic group (68%); however, this difference was not significant (p = 0.39). Fifteen surviving patients (53.6%) have mild/moderate renal impairment (creatinine ≥125 μmol/L). None has severe renal failure (serum creatinine ≥250 μmol/L) or end‐stage renal disease requiring hemodialysis. CLKT has good results in selected groups of patients. It provides protection to kidney allograft in liver‐based metabolic diseases affecting kidney. The rate of acute rejection episodes of kidney is low. Significant proportion develops long‐term mild/moderate renal dysfunction. Careful attention to immunosuppression to minimize nephrotoxicity may help.