Intranasal Midazolam With Lidocaine for Sedation in Pediatric Myringotomy and Tube Surgery: A Randomized Controlled Trial.

BACKGROUND AND AIMS: Intranasal midazolam (INM) sedation for children has been associated with side effects. This prospective, double-blind, placebo-controlled trial assessed whether the addition of lidocaine to INM (INM+L) affected efficacy or discharge time among pediatric patients undergoing elective bilateral myringotomy and tube placement (BMT). METHODS: This trial enrolled children aged between 18 months to seven years undergoing BMT, physical status class 1 or 2, in a single academic medical center. Interventions were placebo (intranasal saline), INM only (0.2mg/kg of INM concentration 5mg/ml), and INM+L (0.2mg/kg INM with addition of lidocaine 4% based on 25% of midazolam volume). Outcomes included post-anesthesia care unit times, observed behavioral distress (OBD) visual analog scale (VAS) (by nurse and parent), and sedation scores by certified registered nurse anesthetist (CRNA) and registered nurse (RN). RESULTS: Forty-two subjects were included, 14 in each group, with 52% female, 41% physical status 2, and an average age of 2.7 years. Post-anesthesia care unit times averaged 36.5 minutes (range 15-132 minutes), with no delay in discharge with INM or INM+L versus placebo (p=0.88). Verbal complaints were highest among INM+L at the time of administration (p=0.01). RN-scored OBD at one minute post administration differed significantly across the three groups (p=0.01). Parental OBD scores did not differ across treatment groups. Agitation was greatest at time of induction of anesthesia in the placebo group (p=0.01). CONCLUSIONS: The addition of licodaine to INM does not adversely influence time to discharge and does not reduce side effects, improve efficacy, or change duration of action of INM.

Rainfall Runoff and Flood Simulations for Hurricane Impacts on Woonasquatucket River, USA.

Integrated hydrological and hydrodynamic modeling study has been conducted to investigate hurricane impact on Woonasquatucket River, Rhode Island, USA. Model simulation was conducted for the case study of 2010 storm event. The hydrological model simulates the runoff from the heavy rainstorm, while the river hydrodynamic model simulates the flood waves affected by the interactions of upstream rainfall runoff and downstream storm surge. Results indicate that the river floods was dominant by rainfall runoff in upper river reaches, but dominant by storm surge in the lower river area near the estuary.

Relation of viscous lidocaine combined with propofol deep sedation during elective upper gastrointestinal endoscopy to discharge.

Fusing topical pharyngeal anesthetics (TPAs) to intravenous sedation during esophagogastroduodenoscopy (EGD) has been controversial. This double-blind, randomized, placebo-controlled trial assessed the association of TPA with patient recovery time, post-EGD to discharge. Supplementary aims were to determine the association of TPA with patient and practitioner satisfaction (both measured on a 100-mm visual analog scale), total propofol dose, and side effects. The study included 93 patients (mean age 53.8 years, range 44-67; 37 men and 56 women) undergoing elective EGD at a single academic medical center from September 2015 to October 2016. Urgent or therapeutic EGDs were excluded. Interventions were 7.5 mL 2% lidocaine viscous solution and 7.5 mL placebo solution (3% methylcellulose). There were no statistically significant differences between the lidocaine (n = 46) and placebo (n = 47) groups with respect to recovery time (42 ± 17.8 vs 39 ± 15.9 minutes; P = 0.23), procedure time (6.5 ± 2.7 vs 7 ± 3.6 minutes; P = 0.77), endoscopist satisfaction (83.2 ± 24.4 vs 77 ± 27.7, P = 0.23), patient discomfort (16.6 ± 19.8 vs 24.0 ± 29.7, P = 0.37), or total propofol administered (2.3 ± 1.3 vs 2.3 ± 1.0 mg/kg, P = 0.55). Compared to placebo, topical viscous lidocaine does not appear to delay recovery time or adversely affect sedation-related outcomes.

Clinicopathological and molecular characteristics of extramedullary acute myeloid leukaemia.

AIMS: Myeloid sarcoma (MS) is a rare extramedullary neoplasm composed of immature myeloid precursor cells thought to be a unique clinical presentation of acute myeloid leukaemia (AML). Like AML, MS has a poor prognosis, but due to the rare nature of MS there are limited studies examining potential prognostic factors. We report our institutional experience, with the aim of investigating and establishing salient clinicopathological and molecular features of MS. METHODS AND RESULTS: We retrospectively examined all clinicopathological and molecular data on MS patients between 2001 and 2017 from the University of Alabama at Birmingham (UAB) electronic medical records. The UAB electronic medical records were also reviewed and compared with the literature for other potential prognostic factors. Sixty-three patients were included in the study. The median overall survival was 24 months in the group with normal karyotype and 12 months in patients with an abnormal karyotype. CONCLUSIONS: We found that an abnormal karyotype was associated with a statistically significant worse prognosis.

PAX8 Expression in Solitary Fibrous Tumor: A Potential Diagnostic Pitfall.

PAX8 is used as a diagnostic aid in classifying retroperitoneal (RP) spindle cell tumors. PAX8 positivity in a spindled RP tumor is typically associated with sarcomatoid renal cell carcinoma (SRCC). However, PAX8 expression in solitary fibrous tumor (SFT), a tumor not uncommon to the RP, has not been extensively studied. We investigated the expression of PAX8 in SFTs and other spindle cell RP tumors. We collected 30 SFT, 23 SRCC, 11 gastrointestinal stromal tumors, 2 synovial sarcomas, 6 dedifferentiated liposarcomas (DDLS), 4 well differentiated liposarcomas (WDLS), and select other tumors. We identified nuclear PAX8 expression in 13 of 30 (43%) SFT, 0 of 6 (0%) DDLS, and 1 of 4 (25%) WDLS. Twenty-eight of 30 (93%) SFT, 0 of 23 (0%) SRCC, 2 of 6 (33%) DDLS, and 1 of 4 (25%) WDLS showed nuclear STAT6 expression. All gastrointestinal stromal tumors were negative for both PAX8 and STAT6. Of the 13 SFT showing PAX8 expression, 8 showed diffuse expression and 5 expressed PAX8 focally. Extrapleural SFTs were more likely to express PAX8 compared with pleural SFTs (10/13; 77% vs. 3/17; 18%, respectively; P=0.00117). Twenty of 23 (87%) SRCC expressed PAX8; the sarcomatoid component of all 23 SRCC was negative for STAT6. Of the other spindle cell tumors studied, 1 of 2 synovial sarcomas and 1 of 2 histiocytic sarcomas showed PAX8 expression. Pathologists should be aware of the potential pitfall of the relatively frequent expression of PAX8 by SFT and STAT6 expression in liposarcoma. PAX8 expression by a spindle cell lesion of RP would not allow distinction between SFT, SRCC, or sclerosing liposarcoma by itself. A STAT6/PAX8 phenotype excludes SRCC.

Histologic findings associated with false-positive multiparametric magnetic resonance imaging performed for prostate cancer detection.

Magnetic resonance imaging (MRI)/ultrasound fusion-targeted biopsy (TB) has been shown to more accurately identify higher-grade prostate cancers compared with standard-of-care systematic sextant prostate biopsy (SB). However, occasional false-positive imaging findings occur. We investigated the histologic findings associated with false-positive prostate MRI findings. A retrospective review was performed on our surgical pathology database from 2014 to 2017 selecting patients with no cancer detected on TB with concurrent SB after at least 1 prior benign SB session. Histologic features evaluated included percentage of core involvement by chronic inflammation, percentage of core composed of stroma, percentage of glands involved by atrophy, and presence of the following features: acute or granulomatous inflammation, stromal nodular hyperplasia, adenosis, squamous metaplasia, basal cell hyperplasia, and presence of skeletal muscle. Histologic findings were compared between TB and concurrent SB. We identified 544 patients who underwent TB. Of these, 41 patients, including 62 targeted lesions, met criteria. Compared with SB tissue, the mean percentage of stroma was increased in TB (P = .02). Basal cell hyperplasia was also found to be more common on TB (P = .02). Both high percentage of stroma (P = .046) and presence of basal cell hyperplasia (P = .038) were independent predictors on multivariate analysis. The combination of high chronic inflammation, high stroma, acute inflammation, and basal cell hyperplasia was associated with TB (P = .001). Atrophic glands and chronic inflammation showed a positive correlation (r = 0.67, P = .003), which was especially seen in high prostate imaging reporting and data system lesions. Specific benign histologic entities are associated with false-positive findings on prostate MRI.

Virtual Reality Analgesia With Interactive Eye Tracking During Brief Thermal Pain Stimuli: A Randomized Controlled Trial (Crossover Design).

In light of growing concerns about opioid analgesics, developing new non-pharmacologic pain control techniques has become a high priority. Adjunctive virtual reality can help reduce acute pain during painful medical procedures. However, for some especially painful medical procedures such as burn wound cleaning, clinical researchers recommend that more distracting versions of virtual reality are needed, to further amplify the potency of virtual reality analgesia. The current study with healthy volunteers explores for the first time whether interacting with virtual objects in Virtual Reality (VR) via "hands free" eye-tracking technology integrated into the VR helmet makes VR more effective/powerful than non-interactive/passive VR (no eye-tracking) for reducing pain during brief thermal pain stimuli. METHOD: Forty eight healthy volunteers participated in the main study. Using a within-subject design, each participant received one brief thermal pain stimulus during interactive eye tracked virtual reality, and each participant received another thermal pain stimulus during non-interactive VR (treatment order randomized). After each pain stimulus, participants provided subjective 0-10 ratings of cognitive, sensory and affective components of pain, and rated the amount of fun they had during the pain stimulus. RESULTS: As predicted, interactive eye tracking increased the analgesic effectiveness of immersive virtual reality. Compared to the passive non-interactive VR condition, during the interactive eye tracked VR condition, participants reported significant reductions in worst pain (p < 0.001) and pain unpleasantness (p < 0.001). Participants reported a significantly stronger illusion of presence (p < 0.001), and significantly more fun in VR (p < 0.001) during the interactive condition compared to during passive VR. In summary, as predicted by our primary hypothesis, in the current laboratory acute pain analog study with healthy volunteers, increasing the immersiveness of the VR system via interactive eye tracking significantly increased how effectively VR reduced worst pain during a brief thermal pain stimulus. Although attention was not directly measured, the pattern of pain ratings, presence ratings, and fun ratings are consistent with an attentional mechanism for how VR reduces pain. Whether the current results generalize to clinical patient populations is another important topic for future research. Additional research and development is recommended.

Postradiation Histiocytic Sarcoma in the Setting of Muir-Torre Syndrome.

Hereditary nonpolyposis colorectal carcinoma (HNPCC) is an autosomal dominant genetic disorder characterized by a predisposition towards colorectal carcinoma and other extracolonic neoplasms. Histiocytic sarcoma (HS) is a very rare hematologic neoplasm characterized by a malignant proliferation of cells with histiocytic differentiation. We present the case of a 62-year-old male with previous diagnosis of MTS who presented with metastatic colorectal adenocarcinoma, bilateral papillary renal cell carcinoma, and a new squamous cell carcinoma of the scalp, treated with resection and adjuvant radiation therapy. After reconstructive surgery for his scalp resection, the patient developed a persistent nonhealing skin defect. A punch biopsy of this nonhealing skin defect and subsequent immunohistochemistry revealed neoplastic histiocytic cells restricted to the epidermis and underlying dermis. The diagnosis of cutaneous histiocytic sarcoma was then rendered. Histiocytic sarcoma is an exceptionally rare malignancy. Consequently, there is no universally agreed upon management protocol for this malignancy. The patient was admitted to hospice and treated with palliative radiation. This case demonstrates the need for awareness of the risk of secondary malignancies in cancer patients in order to facilitate early surgical intervention and optimal treatment.

Therapy-associated myelodysplastic syndrome with monosomy 7 arising in a Muir-Torre Syndrome patient carrying SETBP1 mutation.

Muir-Torre Syndrome (MTS) is a rare hereditary autosomal dominant cancer syndrome and is linked to hereditary non-polyposis colorectal carcinoma (Lynch Syndrome). Individuals develop various skin neoplasms in addition to colorectal, endometrial and upper gastrointestinal malignancies. Therapy-associated myelodysplastic syndrome (T-MDS) is an aggressive hematologic malignancy and is considered a pre-leukemic phase. T-MDS is associated with prior exposure to chemo- and radiotherapy that potentially results in DNA damage. The current case report presents a 74-year-old male MTS patient with prior history of solid tumors and radiation therapy with new onset cytopenia. A subsequent bone marrow biopsy revealed multilineage dysplasia with a high blast count and a diagnosis of high grade T-MDS was rendered. FISH and G-banded karyotype analyses revealed 5q deletion and monosomy 7. This is a unique case of T-MDS arising in the setting of MTS. Secondary malignancies including MDS and acute leukemia may occur in cancer survivors and are often associated with an unfavorable prognosis. This case demonstrates the need to be aware of the risk of secondary hematologic malignancies in cancer patients and a thorough clinical and lab work-up are warranted in patients with persistent or transfusion requiring cytopenia(s).

Clinical Utility and Biologic Implications of Phosphatase and Tensin Homolog (PTEN) and ETS-related Gene (ERG) in Prostate Cancer.

Phosphatase and tensin homolog (PTEN) and ETS-related gene (ERG) mutations are commonly found in prostate cancer. Although mouse studies have demonstrated that PTEN and ERG cooperatively interact during tumorigenesis, human studies examining these genes have been inconclusive. A systematic PubMed search including original articles assessing the pathogenesis of PTEN and ERG in prostate cancer was performed. Studies examining ERG's prognostic significance have conflicting results. Studies examining PTEN and ERG simultaneously found these genes are likely to occur together, but cooperative tumorigenesis functions have not been conclusively established. PTEN mutations are associated with a range of prognostic features. However, the practical clinical utility of this information remains to be determined.

South Greenland ice-sheet collapse during Marine Isotope Stage 11.

Varying levels of boreal summer insolation and associated Earth system feedbacks led to differing climate and ice-sheet states during late-Quaternary interglaciations. In particular, Marine Isotope Stage (MIS) 11 was an exceptionally long interglaciation and potentially had a global mean sea level 6 to 13 metres above the present level around 410,000 to 400,000 years ago, implying substantial mass loss from the Greenland ice sheet (GIS). There are, however, no model simulations and only limited proxy data to constrain the magnitude of the GIS response to climate change during this 'super interglacial', thus confounding efforts to assess climate/ice-sheet threshold behaviour and associated sea-level rise. Here we show that the south GIS was drastically smaller during MIS 11 than it is now, with only a small residual ice dome over southernmost Greenland. We use the strontium-neodymium-lead isotopic composition of proglacial sediment discharged from south Greenland to constrain the provenance of terrigenous silt deposited on the Eirik Drift, a sedimentary deposit off the south Greenland margin. We identify a major reduction in sediment input derived from south Greenland's Precambrian bedrock terranes, probably reflecting the cessation of subglacial erosion and sediment transport as a result of near-complete deglaciation of south Greenland. Comparison with ice-sheet configurations from numerical models suggests that the GIS lost about 4.5 to 6 metres of sea-level-equivalent volume during MIS 11. This is evidence for late-Quaternary GIS collapse after it crossed a climate/ice-sheet stability threshold that may have been no more than several degrees above pre-industrial temperatures.

Pars plana vitrectomy for dystrophic calcification of a silicone intraocular lens in association with asteroid hyalosis.

UNLABELLED: We present a case in which a pars plana vitrectomy (PPV) was performed to halt the progressive dystrophic calcification of an intraocular lens (IOL) and the need for an IOL exchange. With limited follow-up, the patient's visual complaints have resolved, the dystrophic calcification of the IOL has stabilized, and good visual acuity has been retained. To our knowledge, this is the first report of a patient with progressive dystrophic calcification of silicone IOLs in association with asteroid hyalosis treated primarily with a PPV. In certain cases, PPV may be considered in patients with dystrophic calcification in association with asteroid hyalosis and may prevent the need for a late IOL exchange. FINANCIAL DISCLOSURE: Neither author has a financial or proprietary interest in any material or method mentioned.

Worsening essential tremor following deep brain stimulation: disease progression versus tolerance.

A major concern regarding ventralis intermedius nucleus deep brain stimulation for essential tremor has been the loss of surgical efficacy over time in a minority of patients. Some experts have ascribed the worsening tremor to tolerance, while other evidence has suggested that disease progression may play a role. Suboptimal lead placement has also been reported to be a factor in worsening tremor following deep-brain stimulation; however, most authors consider this phenomenon to manifest within a few months of the actual surgery. We aimed to dissect the tolerance versus disease progression issue by analysing preoperative versus long-term post-surgical Fahn-Tolosa-Marin Tremor Rating Scale scores both on and off stimulation among 28 patients who underwent ventralis intermedius nucleus deep brain stimulation and 21 age-matched controls. Of the 28 patients in the treatment arm of the cohort, seven (25%) demonstrated evidence of tremor progression, and had a 34% increase in the tremor score off stimulation at the 36 month follow-up compared with a 32% increase among controls (P = 0.67). In one of the seven patients there was evidence of suboptimal lead placement given the lateral position of the lead, and the motor side effects during threshold testing. This patient demonstrated a loss of stimulation benefit between 24 and 36 months, which may have been more indicative of tolerance. The other six subjects (86%) maintained stimulation benefit throughout the follow-up period, despite worsening tremor off stimulation (at a comparable rate to that of controls), making disease progression the most likely explanation. The data suggest that deep brain stimulation tolerance may be over-reported in the literature, and that a tolerance versus disease progression work-up should include: examining the trend in off stimulation scores, accounting for image based lead locations, and during programming sessions checking for thresholds which may elicit clinical benefits and side effects.

Sr-Nd-Pb isotope evidence for ice-sheet presence on southern Greenland during the Last Interglacial.

To ascertain the response of the southern Greenland Ice Sheet (GIS) to a boreal summer climate warmer than at present, we explored whether southern Greenland was deglaciated during the Last Interglacial (LIG), using the Sr-Nd-Pb isotope ratios of silt-sized sediment discharged from southern Greenland. Our isotope data indicate that no single southern Greenland geologic terrane was completely deglaciated during the LIG, similar to the Holocene. Differences in sediment sources during the LIG relative to the early Holocene denote, however, greater southern GIS retreat during the LIG. These results allow the evaluation of a suite of GIS models and are consistent with a GIS contribution of 1.6 to 2.2 meters to the ≥4-meter LIG sea-level highstand, requiring a significant sea-level contribution from the Antarctic Ice Sheet.

Basics of elder law and legal liabilities of negligence and malpractice for physicians as they apply to individuals with disabilities.

This article provides information regarding the issues that physicians face when dealing with elderly patients with cognitive deficits. It includes a discussion of basic legal terms and concepts that medical personnel should understand, various difficulties encountered by patients and families in crisis situations, and how the legal system deals with these issues. It concludes with a general discussion of the legal liabilities of negligence and malpractice.