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Objectives: To report the expanded neurological presentations and oncological associations of tripartite motif-containing protein 46 (TRIM46)-IgG seropositive patients.Methods: Archived sera/cerebrospinal fluid (CSF) were evaluated by tissue-based immunofluorescence assay to identify patients with identical axon initial segment (AIS)-specific staining pattern. Phage immunoprecipitation sequencing (PhIP-Seq) was used to identify the putative autoantigen.Results: IgG in serum (17) and/or CSF (16) from 25 patients yielded unique AIS-specific staining on murine central nervous system (CNS) tissue. An autoantibody specific for TRIM46 was identified by PhIP-Seq, and autoantigen specificity was confirmed by transfected COS7 cell-based assay. Clinical information was available for 22 TRIM46-IgG seropositive patients. Fifteen were female (68%). Median age was 67 years (range 25-87). Fifteen (68%) patients presented with subacute cerebellar syndrome (six isolated; nine with CNS accompaniments: encephalopathy (three), brainstem signs (two), myelopathy (two), parkinsonism (one)). Other phenotypes included limbic encephalitis (three), encephalopathy with/without seizures (two), myelopathy (two). Eighteen (82%) had cancer: neuroendocrine carcinomas (9; pancreatic (3), small-cell lung (4), oesophagus (1), endometrium (1)), adenocarcinomas (6; lung (2), ovarian (2), endometrial (1), breast (1)), sarcoma (2) and gastrointestinal tumour (1). Neurological symptoms in three followed immune checkpoint inhibitor (ICI) administration.Conclusions: This study supports TRIM46-IgG being a biomarker of paraneoplastic CNS disorders and expands the neurological phenotypes, oncological and ICI-related adverse event associations. [ABSTRACT FROM AUTHOR]

Background: Oncology patients and physicians value empathy because of its association with improved health outcomes. Common measures of empathy lack consistency and were developed without direct input from patients. Because of their intense engagement with health care systems, oncology patients may have unique perspectives on what behaviors signal empathy in a clinical setting.Methods: As part of a cross-sectional study of patient perspectives on clinician empathy at an academic cancer center in the northeastern United States, the authors solicited up to 10 free-text responses to an open-ended question about what clinician behaviors define empathy.Results: The authors categorized open-ended responses from 89 oncology patients into 5 categories representing 14 themes. These categories were relationship sensitivity, focus on the whole person, communication, clinician attributes, and institutional resources and care processes. Frequently represented themes, including listening, understanding, and attention to emotions and what matters most, aligned with existing measures of empathy; behaviors that were not well represented among existing measures included qualities of information sharing and other communication elements. Patients also associated clinician demeanor, accessibility, and competence with empathy.Conclusions: Oncology patients' perspectives on empathy highlight clinician behaviors and attributes that may help to refine patient experience measures and may be adopted by clinicians and cancer centers to enhance patient care and outcomes. High-quality communication skills training can promote active listening and paying attention to the whole person. A system-level focus on delivering empathic care may improve patients' experiences and outcomes.Lay Summary: Oncology patients' responses to an open-ended question about empathic clinician behavior have revealed insights into a variety of behaviors that are perceived as demonstrative of empathy. These include behaviors that imply sensitivity to the clinician-patient relationship, such as listening and understanding and attention to the whole person. Participants valued caring communication and demeanor and clinician accessibility. Perspective taking was not common among answers. Many existing measures of clinical care quality do not include the behaviors cited by patients as empathic. These results can inform efforts to refine quality measures of empathy-associated behaviors in clinical practice. Cancer centers can use skills training to improve elements of communication. [ABSTRACT FROM AUTHOR]

Androgen deprivation therapy (ADT) used for prostate cancer (PCa) management is associated with metabolic and anthropometric toxicity. Metformin given concurrent to ADT is hypothesized to counteract these changes. This planned interim analysis reports the gastrointestinal and genitourinary toxicity profiles of PCa patients receiving ADT and prostate/pelvic radiotherapy plus metformin versus placebo as part of a phase 2 randomized controlled trial. Men with intermediate or high-risk PCa were randomized 1:1 to metformin versus placebo. Both groups were given ADT for 18-36 months with minimum 2-month neoadjuvant phase prior to radiotherapy. Acute gastrointestinal and genitourinary toxicities were quantified using CTCAE v4.0. Differences in ≥ grade 2 toxicities by treatment were assessed by chi-squared test. 83 patients were enrolled with 44 patients randomized to placebo and 39 randomized to metformin. There were no significant differences at any time point in ≥ grade 2 gastrointestinal toxicities or overall gastrointestinal toxicity. Overall ≥ grade 2 gastrointestinal toxicity was low prior to radiotherapy (7.9% (placebo) vs. 3.1% (metformin), p = 0.39) and at the end of radiotherapy (2.8% (placebo) vs 3.1% (metformin), p = 0.64). There were no differences in overall ≥ grade 2 genitourinary toxicity between treatment arms (19.0% (placebo) vs. 9.4% (metformin), p = 0.30). Metformin added to radiotherapy and ADT did not increase rates of ≥ grade 2 gastrointestinal or genitourinary toxicity and is generally safe and well-tolerated. [ABSTRACT FROM AUTHOR]

Objectives: To explore how physicians in neurology, family medicine, internal medicine, and emergency medicine characterize clinical empathy.Methods: Physicians (N = 94) were asked to describe up to 10 examples of empathic physician behavior. Data were analyzed using template analysis.Results: Physicians' descriptions of clinical empathy patterned into three themes: Clinical Performance and Professionalism, Interpersonal Communication, and Clinician Orientation. Clinical Performance and Professionalism sub-themes included physician competency and accessibility; intersection with institutional resources; and spending/making/taking time with patients. Interpersonal Communication sub-themes involved information sharing; verbal and nonverbal approaches; interpersonal sensitivity; physician self-disclosure; and attention to emotion. Clinician Orientation encompassed general physician demeanor and internal thoughts and feelings that might be unobservable by patients. Physicians varied widely in the themes they mentioned in their definition of empathy.Conclusion: Physicians hold diverse notions of clinical empathy. These extend beyond traditional affective and cognitive empathy definitions to include structural elements like team-based care and accessibility after hours. Communication behaviors were perceived as important for demonstrating empathy. Some physician descriptions of empathy may not be perceptible to patients.Practice Implications: Training physicians to engage in behaviors that both they and patients perceive as empathic may lead to higher patient and physician satisfaction. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study is to assess the effect of dexmedetomidine on intraocular pressure (IOP) as an additive in peribulbar injections in glaucoma surgeries.Methods: A prospective, randomized, double-blind, parallel assignment interventional study was conducted for patients undergoing glaucoma surgeries at a tertiary eye care hospital in North India. Patients were randomized to two groups, Dexmed group and Placebo group. In the Dexmed group, dexmedetomidine (0.4 μg/kg body weight) was given as an additive along with peribulbar block. The primary outcome was change in IOP pre- and postperibulbar injections (IOP before the block, and after 5 and 15 min of the block). Secondary outcome measures were onset of block, adverse effects (bradycardia, hypotension, respiratory depression, and level 4 sedation), and surgeon satisfaction.Results: A total of 104 patients were randomized, 52 each in the Dexmed group and Placebo group. The percentage decrease in IOP was significantly more in the Dexmed group than in the Placebo group both at 5 and 15 min' post block (P < 0.05). At 5 min, the mean percent decrease in IOP in Dexmed group was -10.48, whereas it was 2.85 in the Placebo group. At 15 min, the mean percent decrease in IOP was -22.59 and -9.42 in the Dexmed and Placebo group, respectively. There was no significant difference between the two groups in the onset of block and adverse effects. Surgeon satisfaction was significantly greater in the Dexmed group than the Placebo group (P < 0.05).Conclusion: Dexmedetomidine lowers IOP significantly in patients undergoing glaucoma surgeries with safe hemodynamic changes and sedative effect. [ABSTRACT FROM AUTHOR]

The clinical phenotype of leucine-rich glioma-inactivated protein 1 (LGI1) and contactin-associated proteinlike 2 (CASPR2) autoimmunity is well defined in adults. Data for children are limited (<10 cases). Among 13,319 pediatric patients serologically tested for autoimmune neurological disorders (2010-2017), 264 were seropositive for voltage-gated potassium channel-complex-IgG (radioimmunoprecipitation). Only 13 (4.9%) were positive by transfected cell-binding assay for LGI1-IgG (n = 7), CASPR2-IgG (n = 3), or both (n = 3). This is significantly less than in adults. Encephalopathy, seizures, and peripheral nerve hyperexcitability were common, as was coexisting autoimmunity. No faciobrachial dystonic seizures or cancers were identified. Functional neurologic disorders were frequently the initial diagnosis, and immunotherapy appeared beneficial. Ann Neurol 2018;84:473-480. [ABSTRACT FROM AUTHOR]

Background: The subjective sensation of dry mouth, xerostomia, is a well-recognized problem in adults, however, relatively little attention has been paid to this issue in children. Xerostomia commonly occurs as an adverse effect of drugs in asthma and leukemia, which alter the composition and flow of saliva and systemic diseases, including diabetes. It decreases the oral pH and significantly increases the development of plaque and dental caries.Aim: This study aims to evaluate and compare the dental caries status and salivary properties of children aged 5-14 years undergoing treatment for acute lymphoblastic leukemia, type 1 diabetes mellitus, and asthma - in vivo.Materials and Methods: The study was divided into two parts: Part I: Oral examination was performed and dental caries status Decayed, Missing, Filled Teeth/ decayed, extraction, filled teeth (DMFT/deft) was noted and Part II: Salivary analysis was performed by GC Saliva-Check BUFFER kit to check for hydration, viscosity, pH of saliva, salivary flow, and buffering capacity.Statistical Analysis: All statistical analysis was performed using the SPSS 21 statistical software version. Inferential statistics were performed using Chi-square test and ANOVA. Post hoc pairwise comparison was done using Post hoc Tukey's test.Results: The prevalence of mean DMFT/deft with regard to salivary properties was highest in leukemic patients followed in descending order by diabetic and asthmatic patients.Conclusions: Leukemic patients had significantly higher caries and decreased salivary properties while asthmatic patients showed the least caries prevalence and best salivary properties. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study is to determine which parameter of Cirrus and RTVue optical coherence tomography (OCT) has the highest ability to discriminate between early, moderate, and advanced glaucoma. Simultaneously, to compare the performance of the two OCT devices in terms of their ability to differentiate the three stages of glaucoma. Further, to analyze the macular parameters of both devices and compare them with the conventional retinal nerve fiber layer (RNFL) parameters.Methods: One hundred and twenty eyes (30 healthy and 90 glaucomatous [30 mild, 30 moderate, and 30 advanced glaucoma]) of 65 participants (15 healthy, 50 glaucomatous [15 mild, 15 moderate, and 20 advanced glaucoma]) underwent Cirrus and RTVue OCT scanning on a single visit.Results: Average RNFL thickness and superior RNFL thickness of both the devices and inferior (ganglion cell complex [GCC] of RTVue device best differentiated normals from all stage glaucomatous eyes (P > 0.05). Cirrus average RNFL thickness and superior RNFL thickness performed better than other parameters (P < 0.05) in differentiating early glaucoma from moderate and advanced. In differentiating advanced from early and moderate glaucoma, RTVue average, superior, and inferior RNFL thickness and inferior GCC parameters had the highest discriminating ability (P < 0.05).Conclusion: Overall, average RNFL thickness had the highest ability to distinguish different stages of the disease. No significant difference was found between RTVue and Cirrus OCT device in different severity levels. No significant difference was observed between RNFL and macular parameters in different stages of glaucoma. [ABSTRACT FROM AUTHOR]

Objective: Loss of function of the astrocyte-specific protein MLC1 leads to the childhood-onset leukodystrophy "megalencephalic leukoencephalopathy with subcortical cysts" (MLC). Studies on isolated cells show a role for MLC1 in astrocyte volume regulation and suggest that disturbed brain ion and water homeostasis is central to the disease. Excitability of neuronal networks is particularly sensitive to ion and water homeostasis. In line with this, reports of seizures and epilepsy in MLC patients exist. However, systematic assessment and mechanistic understanding of seizures in MLC are lacking.Methods: We analyzed an MLC patient inventory to study occurrence of seizures in MLC. We used two distinct genetic mouse models of MLC to further study epileptiform activity and seizure threshold through wireless extracellular field potential recordings. Whole-cell patch-clamp recordings and K+ -sensitive electrode recordings in mouse brain slices were used to explore the underlying mechanisms of epilepsy in MLC.Results: An early onset of seizures is common in MLC. Similarly, in MLC mice, we uncovered spontaneous epileptiform brain activity and a lowered threshold for induced seizures. At the cellular level, we found that although passive and active properties of individual pyramidal neurons are unchanged, extracellular K+ dynamics and neuronal network activity are abnormal in MLC mice.Interpretation: Disturbed astrocyte regulation of ion and water homeostasis in MLC causes hyperexcitability of neuronal networks and seizures. These findings suggest a role for defective astrocyte volume regulation in epilepsy. Ann Neurol 2018;83:636-649. [ABSTRACT FROM AUTHOR]

Background of the study: Enteral feeding in preterm neonates with intrauterine growth restriction (IUGR) and absent or reversed end diastolic flow (AREDF) on umbilical artery (UA) Doppler is delayed owing to an increased risk of necrotizing enterocolitis (NEC). Delaying enteral feeding with longer duration of parenteral nutrition (PN) carries an increased risk of sepsis.Objectives: To study early versus late feeding in preterm IUGR neonates for time required to attain sufficient feed volume to discontinue PN and increased risk of NEC or feed intolerance (FI).Design: Open-label randomized controlled trial.Setting: Tertiary care neonatal unit and fetal-maternal medicine unit in India.Participants: Preterm intrauterine growth restricted neonates' ≤32 weeks with AREDF on UA Doppler enrolled from 1 January 2014 to 31 July 2015.Intervention: Randomized to receive early or late feeding using mothers own or donor breast milk as per a feed initiation and advancement protocol.Primary outcome: Time in days required to attain sufficient feed volume allowing discontinuation of PN and incidence of NEC in neonates fed early versus late.Results: There were 77 eligible neonates. Sixty-two neonates were included and stratified as extreme preterm (27-29 weeks) (n = 20) and very preterm (30-32 weeks) (n = 42). Ten extreme preterm and 21 very preterm neonates were randomized to each early feeding and late feeding arm. There was a significantly faster attainment of sufficient feeds in the early feeding arm of both the stratified groups [extreme preterm: median 14 days (Interquartile range IQR: 12-15) compared with 18 days (IQR: 18-20), hazard ratio (HR): 1.59, 95% CI: 0.626-4.078; very preterm: 12 days (IQR: 10-14) as compared with 16 days (IQR 15-17), HR: 1.89, 95% CI: 1.011-3.555]. There was no difference in the incidence of NEC, FI and combined outcome of NEC and FI.Conclusion: Early feeding in preterm IUGR neonates with AREDF on antenatal UA Doppler allowed earlier discontinuation of PN, allowing birth weight to be regained earlier and did not increase the incidence of NEC and FI. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the incidence and prevalence of autoimmune encephalitis and compare it to that of infectious encephalitis.Methods: We performed a population-based comparative study of the incidence and prevalence of autoimmune and infectious encephalitis in Olmsted County, Minnesota. Autoimmune encephalitis diagnosis and subgroups were defined by 2016 diagnostic criteria, and infectious encephalitis diagnosis required a confirmed infectious pathogen. Age- and sex-adjusted prevalence and incidence rates were calculated. Patients with encephalitis of uncertain etiology were excluded.Results: The prevalence of autoimmune encephalitis on January 1, 2014 of 13.7/100,000 was not significantly different from that of all infectious encephalitides (11.6/100,000; p = 0.63) or the viral subcategory (8.3/100,000; p = 0.17). The incidence rates (1995-2015) of autoimmune and infectious encephalitis were 0.8/100,000 and 1.0/100,000 person-years, respectively (p = 0.58). The number of relapses or recurrent hospitalizations was higher for autoimmune than infectious encephalitis (p = 0.03). The incidence of autoimmune encephalitis increased over time from 0.4/100,000 person-years (1995-2005) to 1.2/100,000 person-years (2006-2015; p = 0.02), attributable to increased detection of autoantibody-positive cases. The incidence (2.8 vs 0.7/100,000 person-years, p = 0.01) and prevalence (38.3 vs 13.7/100,000, p = 0.04) of autoimmune encephalitis was higher among African Americans than Caucasians. The prevalence of specific neural autoantibodies was as follows: myelin oligodendrocyte glycoprotein, 1.9/100,000; glutamic acid decarboxylase 65, 1.9/100,000; unclassified neural autoantibody, 1.4/100,000; leucine-rich glioma-inactivated protein 1, 0.7/100,000; collapsin response-mediator protein 5, 0.7/100,000; N-methyl-D-aspartate receptor, 0.6/100,000; antineuronal nuclear antibody type 2, 0.6/100,000; and glial fibrillary acidic protein α, 0.6/100,000.Interpretation: This study shows that the prevalence and incidence of autoimmune encephalitis are comparable to infectious encephalitis, and its detection is increasing over time. Ann Neurol 2018;83:166-177. [ABSTRACT FROM AUTHOR]

Background Context: To date, the surgical approaches for the treatment of lumbar spondylolisthesis by transforaminal lumbar interbody fusion (TLIF) using minimally invasive spine surgery assisted with intraoperative computed tomography image-integrated navigation (MISS-iCT), fluoroscopy (MISS-FS), and conventional open surgery (OS) are debatable.Purpose: This study compared TLIF using MISS-iCT, MISS-FS, and OS for treatment of one-level lumbar spondylolisthesis.Study Design: This is a prospective, registry-based cohort study that compared surgical approaches for patients who underwent surgical treatment for one-level lumbar spondylolisthesis.Patient Sample: One hundred twenty-four patients from January 2010 to March 2012 in a medical center were recruited.Outcome Measures: The outcome measures were clinical assessments, including Short-Form 12, visual analog scale (VAS), Oswestry Disability Index, Core Outcome Measurement Index, and patient satisfaction, and blood loss, hospital stay, operation time, postoperative pedicle screw accuracy, and superior-level facet violation.Methods: All surgeries were performed by two senior surgeons together. Ninety-nine patients (40M, 59F) who had at least 2 years' follow-up were divided into three groups according to the operation methods: MISS-iCT (N=24), MISS-FS (N=23), and OS (N=52) groups. Charts and surgical records along with postoperative CT images were assessed.Results: MISS-iCT and MISS-FS demonstrated a significantly lowered blood loss and hospital stay compared with OS group (p<.01). Operation time was significantly lower in the MISS-iCT and OS groups compared with the MISS-FS group (p=.002). Postoperatively, VAS scores at 1 year and 2 years were significantly improved in the MISS-iCT and MISS-FS groups compared with the OS groups. No significant difference in the number of pedicle screw breach (>2 mm) was found. However, a lower superior-level facet violation rate was observed in the MISS-iCT and OS groups (p=.049).Conclusions: MISS-iCT TLIF demonstrated reduced operation time, blood loss, superior-level facet violation, hospital stay, and improved functional outcomes compared with the MISS-FS and OS approaches. [ABSTRACT FROM AUTHOR]

Objective: To study MAMLD1 gene polymorphisms, serum LH and testosterone levels amongst Indian children with isolated hypospadias (IH) and controls.Materials and Methods: Screening of the MAMLD1 gene was performed by PCR sequencing method in 100 Indian children aged 0-12 years presenting with IH and 100 controls. LH and testosterone hormone levels were also assessed (categorized in four age-wise groups).Results: IH subjects had significantly higher incidence of MAMLD1 polymorphism as compared to controls (33 vs 15 %, p = 0.01). Of various genomic variants identified in this study, the noteworthy novel ones were missense mutation P299A and single nucleotide polymorphism c.2960C>T in 3' UTR of Exon 7. While p 299A was found to cause protein structural instability consequent to amino acid change, eighty percent subjects with c.2960C>T in 3' UTR of Exon 7 (corresponding to newly discovered currently non-validated exon 11) were found to have lower testosterone levels when compared with their age group mean. IH showed statistically higher incidence of c.2960C>T in comparison to controls (22 vs 10 %, p value 0.046) and about 2.5-folds higher risk of this anomaly.Conclusion: Occurrence of MAMDL1 gene polymorphisms, specially of c.2960C>T in 3' UTR of its exon 7 is associated with a higher risk of IH in Indian children, probably by lowering androgenic levels. [ABSTRACT FROM AUTHOR]

Introduction: Heterogeneity of presenting symptoms makes the initial clinical diagnosis of Guillain-Barré syndrome (GBS) challenging.Methods: Observational retrospective study from 2 teaching hospitals (Parkland Memorial Hospital and University of Texas Southwestern University Hospital) between 2008 and 2013.Results: Sixty-nine GBS patients were identified. GBS was suspected on initial emergency department visit in only 49%. During first hospital encounter, 58% were evaluated by a neurologist. Neuropathic pain and presence of intact deep tendon reflexes were associated with delayed GBS diagnosis (P < 0.05). There was significantly better clinical outcome among patients who were evaluated by a neurologist during the initial visit (P < 0.005). Among these patients there was also significant difference in discharge destination; 71.2% of patients evaluated by a neurologist were discharged home (P < 0.01). Patients in whom GBS was not suspected at the time of initial Neurology evaluation were more likely to require intubation and to have residual weakness at the time of discharge (P < 0.05).Conclusions: Atypical clinical signs and symptoms may lead to delayed diagnosis of GBS. Early neurological evaluation is associated with improved clinical diagnosis and discharge disposition. [ABSTRACT FROM AUTHOR]

Context: Sodium hypochlorite is the most widely used irrigant in endodontic practice, but it has various disadvantages. Literature has shown that herbal products such as Propolis, Azadirachta indica (AI), Triphala, Curcuma longa, and Morinda citrifolia (MC) possess good antimicrobial properties and thus can be used as potential endodontic irrigants.Aim: To evaluate and compare the antimicrobial activity of five herbal extracts, i.e., Propolis, AI, Triphala, C. longa, and MC with that of 2.5% sodium hypochlorite against Enterococcus faecalis.Materials and Methods: E. faecalis American Type Culture Collection 21292 was inoculated onto brain heart infusion agar plate. Discs impregnated with herbal medicaments were placed on the inoculated plates and incubated at 37°C aerobically for 24 h and growth inhibition zones were measured.Statistical Analysis: Mean zone of inhibition in descending order was found as sodium hypochlorite > Propolis > AI > Triphala > C. longa = MC > ethanol. Statistical analysis was performed using one-way analysis of variance which showed a significant difference in the zone of inhibition of sodium hypochlorite and Propolis (P < 0.001).Results: Propolis showed highest zone of inhibition among all the herbal extracts next to sodium hypochlorite.Conclusion: Propolis and AI have significant antimicrobial activity against E. faecalis. [ABSTRACT FROM AUTHOR]

Unlabelled: The objective of the study was to compare the effect of umbilical cord milking (UCM) and delayed cord clamping (DCC) on hematological parameters (serum ferritin and hemoglobin) at 6 weeks of life in term neonates. It was a randomized controlled trail conducted at a teaching hospital in North India during August 2012 to August 2013. Babies born at >36 weeks of gestation were randomized in two groups, UCM and DCC (100 in each group). Umbilical cord milking was done after cutting and clamping the cord at 25 cm from the umbilicus. In DCC group, clamping was delayed by 60 to 90 s before cutting the cord. The baseline characteristics were comparable in the two groups. Mean serum ferritin (134.0 ng/ml [89.8]) and mean hemoglobin (11.0 gm/dl [2.4]) in umbilical cord milking group was comparable to mean serum ferritin (142.7 ng/ml [87.1]) and hemoglobin (11.3 gm/dl [2.6]) in DCC group at 6 weeks of age. There was no difference in hemodynamic status, cranial Doppler indices, and adverse neonatal outcomes among the two groups.Conclusion: In term neonates, the DCC and UCM had comparable effect on hematological parameters at 6 weeks of life.What Is Known: • Delayed cord blood clamping improves certain hematologic parameters for neonates, which is potentially important in populations with high rates of neonatal and childhood anemia, but that delayed cord blood clamping may not be feasible in clinical situations when neonatal resuscitation is urgent.What Is New: • There is no significant difference in ferritin and hemoglobin levels at 6 weeks among term, Indian neonates who had UCM and DCC and that this study may give support to the practice of UCM in term deliveries when DCC is not feasible. [ABSTRACT FROM AUTHOR]

Objective: To compare tympanic membrane temperature and rectal temperature in febrile pediatric patients.Methods: Sixty febrile children were enrolled as continuous enrollment at initial triage. Two readings of ear temperature were taken in each child with Thermoscan infrared thermometer. Rectal temperature was recorded by a digital electronic thermometer. Comparison of both the techniques was done and co-relation co-efficients calculated. Parental preference for both techniques was assessed.Results: It was observed that mean ear temperature was 38.9+/-0.90 C and that for rectal temperature was 38.8+/-0.80 degrees C. The correlation coefficient between the two was 0.994 (p < 0.01). Coefficients for both sites were comparable over a wide age range. The difference between readings taken from two ears was not significant. Temperature ranges over which readings were recorded were quite wide for both techniques. Parental preference for tympanic thermometry over rectal thermometry was noticed. Tympanic thermometry utilizes pyro-electric sensors, to detect infra-red rays emitted from the surface of tympanic membrane. Ear temperatures correlates well with rectal temperatures which have long been considered as "core" temperatures. Parents prefer the technique of ear thermometry which is quick (2 sec), safe and non-invasive and patient resistance for this is also less.Conclusion: A non-invasive, non-mucous device which is accurate over a wide range of temperature could be very useful. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the outcomes of three surgical techniques for the closure of urethrocutaneous fistula (UCF) after hypospadias repair.Materials and Methods: Fifty-one patients (mean age 6.5 years) who underwent UCF closure between June 1998 and February 2008 were divided in to three groups depending on fistula size; group I had <2 mm and (n = 17, 33.4%), group II had 2-4 mm (n = 21, 41.2%) and group III had >4 mm or multiple fistulas (n = 13, 25.4%). Group I patients were treated by excision and simple closure. Patients in group II and III were treated with flip flap technique along with the wrapping of repaired area with scrotal dartos flap and tunneled tunica vaginalis flap (TVF), respectively.Results: Mean surgical time was 45 min (range 30-55), 60 min (range 50-75) and 80 min (range 60-100) in three techniques, respectively. The mean follow-up was 3.5 years (range 6 months-10 years). No patient had recurrence of fistula in group III, while 2 (9.5%) and 4 (25.4%) patients in groups II and I, respectively, had recurrent UCF. No postoperative complications were encountered in the testis or the scrotum. No patient had torsion or deviation of penis.Conclusion: Simple fistula closure carries a higher risk of recurrence even in small sized fistulas. The application of scrotal dartos or TVF for wrapping the repaired area gives excellent results and they are easy to harvest with no harmful effects on the scrotum or testis. [ABSTRACT FROM AUTHOR]

The hepatic venous pressure gradient (HVPG) clearly reflects portal pressure in cirrhotic portal hypertension. Its relation with variceal bleeding has been well studied. We undertook to study the relation of HVPG to variceal size, Child's status, and etiology of cirrhosis. Patients with cirrhotic portal hypertension with esophageal varices underwent HVPG measurement as part of a prospective evaluation. One hundred seventy-six cirrhotics with varices (M:F, 140:36; mean age, 42.6 +/- 13.4 years), 104 with CLD related to viral etiology, 40 with alcoholic liver disease, 26 cryptogenic with cirrhosis, and 6 with miscellaneous causes of CLD underwent HVPG measurement. The mean HVPG was lower in patients with small varices (n = 77; 14.6 +/- 5.9 mm Hg) than in patients with large varices (n = 99; 19.2 +/- 6.6 mm Hg; P < 0.01). In patients with large varices, the mean HVPG in bleeders (n = 37) was higher than in nonbleeders (n = 62) (21.7 +/- 7.2 vs 17.9 +/- 6.2 mm Hg; P < 0.01). The mean HVPG was significantly higher in Child's B (n = 97; 17.4 +/- 6.9 mm Hg) and C (n = 56; 19.0 +/- 5.7 mm Hg) compared to Child's A cirrhotics (n = 23; 12.2 +/- 5.9 mm Hg; P < 0.01), and Child's C compared to Child's B cirrhotics (P = 0.05). HVPG was higher in alcoholic compared to nonalcoholic cirrhotics (20.8 +/- 7.3 vs 16.4 +/- 6.3 mm Hg; P < 0.05), but this was not significant in multivariate analysis. The HVPG was comparable between hepatitis B- and hepatitis C virus-related cirrhotics (P = 0.8). Cirrhotics with ascites had a higher HVPG than those without ascites (18.5 +/- 5.6 vs 16.6 +/- 7.6 mm Hg; P = 0.02). In multivariate analysis, only Child's status, size of varices, and variceal bleed predicted higher HVPG. HVPG is higher in cirrhotics with large varices and a history of bleed. There is a good correlation between HVPG and large varices, bleeder status, and ascites. A higher HVPG reflects more severe liver disease. The etiology of liver disease did not influence the portal pressure. [ABSTRACT FROM AUTHOR]

Purpose: Previous experience with perillyl alcohol (POH) was with a formulation of 500-mg capsules each containing 250 mg POH and soybean oil. This formulation resulted in the ingestion of large amounts of soybean oil (>10 g/day). Dose-limiting toxicities (DLT) were primarily gastrointestinal. Prior studies also showed no further increase in POH metabolite concentrations with doses of >1600 mg/m2. Therefore, a new formulation of POH was developed (700 mg containing 675 mg POH) in an effort to improve dose and metabolite concentrations delivered and toxicity encountered with chronic dosing.Experimental Design: Eligible patients had refractory solid malignancies. Dose escalation occurred in cohorts of three at the dose levels/dose of 1350 mg, 2025 mg, 2700 mg, 3375 mg and 4050 mg, administered orally four times a day in a 28-day cycle.Results: A group of 19 patients were enrolled. One DLT occurred at dose level 5. This cohort was expanded to six patients, and no further DLT occurred. The maximum tolerated dose was not reached. The predominant toxicity was gastrointestinal. Nausea and vomiting occurred in 63% of patients (12/19, grade 1 in 10). The same proportion of patients (12/19) experienced heartburn and indigestion, primarily grade 1. Although the side effects were mild in nature, three patients withdrew from treatment, citing intolerable gastrointestinal toxicity. The AUCs of POH metabolites did not appear to increase from level 1 to level 2 or change significantly from day 1 to day 29. Inter- and intrapatient variability in metabolite levels was observed.Conclusions: This reformulation of POH appears to be an improvement upon the prior formulation, by reducing the number of capsules ingested and the degree of gastrointestinal toxicity per dose. It does not appear to offer any metabolite pharmacokinetic advantage. A dose of 2050 mg administered four times daily was easily tolerated. Higher doses can be administered but with increasing gastrointestinal toxicity that limits compliance. [ABSTRACT FROM AUTHOR]

Background: The standard of care for locoregional renal cell carcinoma is surgery, but many patients experience recurrence. The objective of the current study was to determine if adjuvant atezolizumab (vs placebo) delayed recurrence in patients with an increased risk of recurrence after resection.Methods: IMmotion010 is a randomised, double-blind, multicentre, phase 3 trial conducted in 215 centres in 28 countries. Eligible patients were patients aged 18 years or older with renal cell carcinoma with a clear cell or sarcomatoid component and increased risk of recurrence. After nephrectomy with or without metastasectomy, patients were randomly assigned (1:1) to receive atezolizumab (1200 mg) or placebo (both intravenous) once every 3 weeks for 16 cycles or 1 year. Randomisation was done with an interactive voice-web response system. Stratification factors were disease stage (T2 or T3a vs T3b-c or T4 or N+ vs M1 no evidence of disease), geographical region (north America [excluding Mexico] vs rest of the world), and PD-L1 status on tumour-infiltrating immune cells (<1% vs ≥1% expression). The primary endpoint was investigator-assessed disease-free survival in the intention-to-treat population, defined as all patients who were randomised, regardless of whether study treatment was received. The safety-evaluable population included all patients randomly assigned to treatment who received any amount of study drug (ie, atezolizumab or placebo), regardless of whether a full or partial dose was received. This trial is registered with ClinicalTrials.gov, NCT03024996, and is closed to further accrual.Findings: Between Jan 3, 2017, and Feb 15, 2019, 778 patients were enrolled; 390 (50%) were assigned to the atezolizumab group and 388 (50%) to the placebo group. At data cutoff (May 3, 2022), the median follow-up duration was 44·7 months (IQR 39·1-51·0). Median investigator-assessed disease-free survival was 57·2 months (95% CI 44·6 to not evaluable) with atezolizumab and 49·5 months (47·4 to not evaluable) with placebo (hazard ratio 0·93, 95% CI 0·75-1·15, p=0·50). The most common grade 3-4 adverse events were hypertension (seven [2%] patients who received atezolizumab vs 15 [4%] patients who received placebo), hyperglycaemia (ten [3%] vs six [2%]), and diarrhoea (two [1%] vs seven [2%]). 69 (18%) patients who received atezolizumab and 46 (12%) patients who received placebo had a serious adverse event. There were no treatment-related deaths.Interpretation: Atezolizumab as adjuvant therapy after resection for patients with renal cell carcinoma with increased risk of recurrence showed no evidence of improved clinical outcomes versus placebo. These study results do not support adjuvant atezolizumab for treatment of renal cell carcinoma.Funding: F Hoffmann-La Roche and Genentech, a member of the Roche group. [ABSTRACT FROM AUTHOR]

The aim of this prospective cross-over study was to investigate the effect of two low-dosed oral contraceptives on markers of endothelial function and plasma lipids. Twelve healthy, nonsmoking women (mean age: 21.7 years) were recruited from the family planning clinic of the university hospital Zurich. For 6 months the participants received a treatment with two contraceptive pills containing 30 μg ethinyl estradiol/150 μg levonorgestrel (three cycles) and 30 μg ethinyl estradiol/75 μg gestodene (three cycles). Plasma levels of endothelin-1, nitric oxide, cholesterol, and HDL were measurement before and during treatment with both oral contraceptive treatments.No significant changes in the plasma levels of nitric oxide and endothelin-1, both important regulators of the vascular tone, were observed during oral contraceptive use. A significant negative correlation was found between nitric oxide and endothelin-1 and nitric oxide and cholesterol. There was a positive correlation between endothelin-1 and cholesterol. In conclusion, the investigated contraceptive pills did not cause major changes in circulating nitric oxide and endothelin-1 plasma levels. [Copyright &y& Elsevier]

Purpose: To report findings from an in vivo dosimetry program implemented for all stereotactic body radiation therapy patients over a 31-month period and discuss the value and challenges of utilizing in vivo electronic portal imaging device (EPID) dosimetry clinically.Methods and Materials: From December 2013 to July 2016, 117 stereotactic body radiation therapy-volumetric modulated arc therapy patients (100 lung, 15 spine, and 2 liver) underwent 602 EPID-based in vivo dose verification events. A developed model-based dose reconstruction algorithm calculates the 3-dimensional dose distribution to the patient by back-projecting the primary fluence measured by the EPID during treatment. The EPID frame-averaging was optimized in June 2015. For each treatment, a 3%/3-mm γ comparison between our EPID-derived dose and the Eclipse AcurosXB-predicted dose to the planning target volume (PTV) and the ≥20% isodose volume were performed. Alert levels were defined as γ pass rates <85% (lung and liver) and <80% (spine). Investigations were carried out for all fractions exceeding the alert level and were classified as follows: EPID-related, algorithmic, patient setup, anatomic change, or unknown/unidentified errors.Results: The percentages of fractions exceeding the alert levels were 22.6% for lung before frame-average optimization and 8.0% for lung, 20.0% for spine, and 10.0% for liver after frame-average optimization. Overall, mean (± standard deviation) planning target volume γ pass rates were 90.7% ± 9.2%, 87.0% ± 9.3%, and 91.2% ± 3.4% for the lung, spine, and liver patients, respectively.Conclusions: Results from the clinical implementation of our model-based in vivo dose verification method using on-treatment EPID images is reported. The method is demonstrated to be valuable for routine clinical use for verifying delivered dose as well as for detecting errors. [ABSTRACT FROM AUTHOR]