Combined Corneal Transplant, Glaucoma Drainage Implantation, and Pars Plana Vitrectomy Outcomes in a Pediatric Population.

PURPOSE: The combination of glaucoma drainage device (GDI), pars plana vitrectomy (PPV), and corneal transplantation is well reported in adults. However, little is known about the outcomes of such combined procedures in pediatric patients. We present a retrospective, single-center study to evaluate the safety and outcomes of concurrent GDI and/or PPV with corneal transplantation in patients 18 years and younger. METHODS: Retrospective chart review of pediatric patients (aged 0-18 years) who received either corneal transplants or keratoprosthesis in combination with at least 1 additional procedure (either GDI and/or PPV) at the Illinois Eye and Ear Infirmary, Chicago, IL, between 2003 and 2017. Primary outcomes included vision, intraocular pressure, and cup-to-disc ratio (C/D). Secondary outcomes included the number of repeat surgeries and intraoperative and postoperative complications. RESULTS: Thirty-six patients were included with a mean age of 8.4 years and an average follow-up of 49.7 months. Nineteen patients received corneal surgery, GDI, and PPV; 4 received corneal and GDI surgery; and 13 received corneal and PPV surgery. Of the 19 patients with all 3 procedures, 48% experienced an increase in vision with an average improvement of 0.9 lines at the last follow-up. Intraocular pressure decreased by an average of -7.2 mm Hg for all groups. Fifty-three percent of all patients experienced complications. CONCLUSIONS: Combined keratoplasty, GDI, and PPV seems to be effective in the management of complex pediatric eye disease. However, owing to the high risk of complications in this vulnerable patient population, careful consideration must be taken when determining a patient's surgical candidacy for combined cornea/glaucoma/retina procedures.

Conjoint adolescent developmental trajectories of alcohol and marijuana use and early adult outcomes among North American Indigenous people.

OBJECTIVE: The current study examined the developmental interrelationships between alcohol and marijuana use trajectories from ages 10 to 18 years in a sample of North American Indigenous adolescents. Distinct co-use groups were formed to create profiles of young adult outcomes. METHOD: Dual group-based trajectory models of marijuana and alcohol frequency were estimated using data from a longitudinal community-based participatory study of Indigenous adolescents from the upper Midwest and Canada. Joint probabilities were used to create co-use groups, and profiles were created using early adult (Mean Age - 26.28 years) outcomes. RESULTS: Four joint trajectory groups were identified: 1) no marijuana and no/low alcohol use (34.4%), 2) mid-onset alcohol only (14%), 3) mid-onset co-use starting at age 13 (24%), and 4) early-onset co-use starting at age 11 (22%). High probabilities existed that adolescents would use marijuana early if they began drinking alcohol at the youngest ages, and that adolescents would not use marijuana if they drank infrequently or delayed drinking until mid-adolescence. Adult outcomes were poorer for the early- and mid-onset co-use groups, but there were few differences between the no/low use and alcohol-only groups. CONCLUSION: Co-use of marijuana and alcohol was associated with poorer outcomes in early adulthood, particularly for the group with an earlier age of onset. Abstaining from either substance in adolescence was associated with better outcomes.

Regional Control and Chemoradiotherapy Dose Response for Clinically Involved Lymph Nodes in Patients with Locally Advanced Endometrial Cancers Who are Not Candidates for Upfront Surgical Staging Extrafascial Hysterectomy.

AIMS: There are limited data in endometrial cancer for nodal control and appropriate treatment volume for non-surgically resected nodes treated with chemoradiotherapy (CRT) for patients who are not candidates for upfront extrafascial hysterectomy. MATERIALS AND METHODS: Patients (n = 105) with clinical stage ≥ II endometrial cancer who were not candidates for upfront extrafascial hysterectomy treated with preoperative CRT were retrospectively reviewed. CRT included pelvic nodes to the common iliac for node-negative disease and para-aortic nodes to the renal vessel for any node-positive disease. Involved nodes most commonly received a boost of 55 Gy in 25 fractions ± additional 4-6 Gy sequential boost for nodes >2 cm. RESULTS: Of the included 95 patients, 55 patients were node positive, with a total of 300 positive nodes. At a median follow-up of 25 months (interquartile range 9-46), the 3-year regional control was 91%. The 3-year involved nodal control rate was 96%. Involved nodal control was significantly higher in type I histology, nodes <2 cm and by radiation dose (75% for <55 Gy, 98% for 55 Gy in 25 fractions and 89% for >55 Gy, P = 0.03). The 3-year para-aortic failure rate for node negative patients treated with pelvis-only CRT was significantly higher with positron emission tomography/computed tomography (PET/CT) versus computed tomography (CT)-based staging (0% versus 20%). CONCLUSION: This is the largest study examining regional control rates of involved lymph nodes with CRT for patients who were not candidates for upfront extrafascial hysterectomy. Nodal failure was low following CRT and dose ≥55 Gy in 25 fractions seems to be adequate for involved nodes.

New pyridine and chromene scaffolds as potent vasorelaxant and anticancer agents.

Based on studies that have reported the association between cancer and cardiovascular diseases, new series of pyridine- (3a-o) and/or chromene- (4a-e) carbonitrile analogous were designed, synthesized and screened for their vasodilation and cytotoxic properties. The majority of the new chemical entities demonstrated significant vasodilation efficacies, compounds 3a, 3h, 3j, 3m, 3o, 4d and 4e exhibited the most promising potency with IC50 = 437.9, 481.0, 484.5, 444.8, 312.1, 427.6 and 417.2 µM, respectively, exceeding prazosin hydrochloride (IC50 = 487.3 µM). Compounds 3b-e, 3k and 3l also, revealed moderate vasodilation activity with IC50 values ranging from 489.7 to 584.5 µM. In addition, the anti-proliferative activity evaluation of the experimental compounds at 10 µM on the MCF-7 and MDA-MB 231 breast cancer cell lines illustrated the excellent anti-proliferative properties of derivatives 3d, 3g and 3i. Compound 3d was the most potent analogue with IC50 = 4.55 ± 0.88 and 9.87 ± 0.89 µM against MCF-7 and MDA-MB 231, respectively. Moreover, compound 3d stimulated apoptosis and cell cycle arrest at the S phase in MCF-7 cells in addition to its capability in accumulation of cells in pre-G1 phase and activating caspase-3. Furthermore, the molecular docking of 3d was performed to discover the binding modes within the active site of caspase-3. 3d, as the only common bi-functional agent among the tested hits, demonstrated that new pyridine-3-carbonitrile derivatives bearing cycloheptyl ring systems offer potential as new therapeutic candidates with combined vasodilation and anticancer properties.

Sec-Delivered Effector 1 (SDE1) of 'Candidatus Liberibacter asiaticus' Promotes Citrus Huanglongbing.

Sec-delivered effector 1 (SDE1) from the huanglongbing (HLB)-associated bacterium 'Candidatus Liberibacter asiaticus' was previously characterized as an inhibitor of defense-related, papain-like cysteine proteases in vitro and in planta. Here, we investigated the contributions of SDE1 to HLB progression. We found that SDE1 expression in the model plant Arabidopsis thaliana caused severe yellowing in mature leaves, reminiscent of both 'Ca. L. asiaticus' infection symptoms and accelerated leaf senescence. Induction of senescence signatures was also observed in the SDE1-expressing A. thaliana lines. These signatures were apparent in older leaves but not in seedlings, suggesting an age-associated effect. Furthermore, independent lines of transgenic Citrus paradisi (L.) Macfadyen (Duncan grapefruit) that express SDE1 exhibited hypersusceptibility to 'Ca. L. asiaticus'. Similar to A. thaliana, transgenic citrus expressing SDE1 showed altered expression of senescence-associated genes, but only after infection with 'Ca. L. asiaticus'. These findings suggest that SDE1 is a virulence factor that contributes to HLB progression, likely by inducing premature or accelerated senescence in citrus. This work provides new insight into HLB pathogenesis.[Formula: see text] Copyright © 2020 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.

Simulating vascular leakage on optical coherence tomography angiography using an overlay technique with corresponding thickness maps.

BACKGROUND: To demonstrate a technique for using optical coherence tomography angiography (OCTA) to simulate leakage in eyes with diabetic macular oedema and determine the sensitivity and positive predictive value of detecting leaking microvasculature on OCTA using fluorescein angiography (FA) as the comparative norm. METHODS: 6×6 mm OCT angiograms were overlaid with the corresponding OCT thickness maps. Microvascular abnormalities on the OCT angiogram underlying areas of thickening on the OCT thickness map were assumed to be leaking. Two independent readers blindly read the OCTA overlay images then the FA images cropped to the same approximate region to delineate areas of leaking microvasculature. The results were compared to determine the sensitivity and positive predictive value of OCTA for detection of leaking vessels. RESULTS: 28 eyes of 19 diabetic patients were included. Each eye demonstrated an average of seven leaking microvascular abnormalities on the OCTA images and 22 leaking abnormalities on the FA images. Sensitivity of leaking microvasculature detection by OCTA was 26.1% and positive predictive value was 68.4%. The correlation coefficient of the two readers' detection of leaking microvasculature was 0.605 for OCTA reads compared with 0.916 for FA. CONCLUSION: OCTA as a whole can be used to simulate leakage, but currently, sensitivity of the technique is low. Further understanding of the OCTA technology may yield novel means of detecting retinal pathology.

Pathologic Features of Down Syndrome Myelodysplastic Syndrome and Acute Myeloid Leukemia: A Report From the Children's Oncology Group Protocol AAML0431.

CONTEXT.­: Detailed diagnostic features of acute myeloid leukemia in Down syndrome are lacking, leading to potential misdiagnoses as standard acute myeloid leukemia occurring in patients with Down syndrome. OBJECTIVE.­: To evaluate diagnostic features of acute myeloid leukemia and myelodysplastic syndrome in patients with Down syndrome. DESIGN.­: Diagnostic bone marrow samples from 163 patients enrolled in the Children's Oncology Group study AAML0431 were evaluated by using central morphologic review and institutional immunophenotyping. Results were compared to overall survival, event-free survival, GATA1 mutation status, cytogenetics, and minimal residual disease results. RESULTS.­: Sixty myelodysplastic syndrome and 103 acute myeloid leukemia samples were reviewed. Both had distinctive features compared to those of patients without Down syndrome. They showed megakaryocytic and erythroid but little myeloid dysplasia, and marked megakaryocytic hyperplasia with unusual megakaryocyte morphology. In acute myeloid leukemia cases, megakaryoblastic differentiation of blasts was most common (54 of 103, 52%); other cases showed erythroblastic (11 of 103, 11%), mixed erythroid/megakaryoblastic (20 of 103, 19%), or no differentiation (10 of 103, 10%). Myelodysplastic syndrome and acute myeloid leukemia cases had similar event-free survival and overall survival. Leukemic subgroups showed interesting, but not statistically significant, trends for survival and minimal residual disease. Cases with institutional diagnoses of French American British M1-5 morphology showed typical features of Down syndrome disease, with survival approaching that of other cases. CONCLUSIONS.­: Myelodysplastic syndrome and acute myeloid leukemia in Down syndrome display features that allow discrimination from standard cases of disease. These distinctions are important for treatment decisions, and for understanding disease pathogenesis. We propose specific diagnostic criteria for Down syndrome-related subtypes of acute myeloid leukemia and myelodysplastic syndrome.

Management of Congenital Aniridia-Associated Keratopathy: Long-Term Outcomes from a Tertiary Referral Center.

PURPOSE: To report the outcomes of medical and surgical management for congenital aniridia-associated keratopathy (AAK) over a long-term follow-up period. DESIGN: Retrospective, comparative case series. METHODS: Medical records of patients diagnosed with congenital aniridia were retrospectively reviewed. Age, sex, ethnicity, follow-up time, AAK stage, noncorneal abnormalities, ocular surgeries, and complications were recorded. The visual acuity equivalent (VAE), approximate Early Treatment Diabetic Retinopathy Study (appETDRS) letter score, was calculated using recorded Snellen visual acuities. RESULTS: A total of 92 eyes of 47 patients (31 females) with mean age of 48.0 ± 18.0 years and mean follow-up of 78.6 ± 42.2 months were included. At the initial visit, 12 eyes (13%) were classified as Stage I AAK, 33 eyes (35.9%) were Stage II, 25 eyes (27.2%) were Stage III, 17 eyes (18.5%) were Stage IV, and 5 eyes (5.4%) were Stage V. Limbal stem cell transplantation (LSCT) and Boston keratoprosthesis (KPro) were frequently performed in eyes with Stages III-V. These advanced corneal surgeries significantly improved the median (95% confidence interval [CI]) of calculated appETDRS scores from 2 (0-20) to 26 (15-41) (Snellen values, 20/20,000 to 20/300; P = 0.0004). Patients with earlier Stages (I-II) of AAK were managed medically and had stable visual acuity through their final visits (appETDRS score of 26 [20-35] to 35 [26-35]; Snellen, 20/300 to 20/200; P > 0.05). The appETDRS VAE was significantly improved from 20 (0-35) to 30 (20-55), Snellen, 20/400 to 20/250, following LSCT (P = 0.021) and from 2 (0-20) to 2 (0-41) after KPro; Snellen, 20/20,000 VAE but with improved 95% CI after follow-up (P = 0.019). CONCLUSIONS: With proper characterization and staging of AAK, individualized medical and advanced surgical interventions preserves and improves visual acuity.

Contrasting effects of high-intensity photosynthetically active radiation on two bloom-forming dinoflagellates.

While light limitation can inhibit bloom formation in dinoflagellates, the potential for high-intensity photosynthetically active radiation (PAR) to inhibit blooms by causing stress or damage has not been well-studied. We measured the effects of high-intensity PAR on the bloom-forming dinoflagellates Alexandrium fundyense and Heterocapsa rotundata. Various physiological parameters (photosynthetic efficiency Fv /Fm , cell permeability, dimethylsulfoniopropionate [DMSP], cell volume, and chlorophyll-a content) were measured before and after exposure to high-intensity natural sunlight in short-term light stress experiments. In addition, photosynthesis-irradiance (P-E) responses were compared for cells grown at different light levels to assess the capacity for photophysiological acclimation in each species. Experiments revealed distinct species-specific responses to high PAR. While high light decreased Fv /Fm in both species, A. fundyense showed little additional evidence of light stress in short-term experiments, although increased membrane permeability and intracellular DMSP indicated a response to handling. P-E responses further indicated a high light-adapted species with Chl-a inversely proportional to growth irradiance and no evidence of photoinhibition; reduced maximum per-cell photosynthesis rates suggest a trade-off between photoprotection and C fixation in high light-acclimated cells. Heterocapsa rotundata cells, in contrast, swelled in response to high light and sometimes lysed in short-term experiments, releasing DMSP. P-E responses confirmed a low light-adapted species with high photosynthetic efficiencies associated with trade-offs in the form of substantial photoinhibition and a lack of plasticity in Chl-a content. These contrasting responses illustrate that high light constrains dinoflagellate community composition through species-specific stress effects, with consequences for bloom formation and ecological interactions within the plankton.

Thomas A. Swift's Electric Rifle Injuries to the Eye and Ocular Adnexa: The Management of Complex Trauma.

PURPOSE: To report the ocular and adnexal injuries sustained by patients with Thomas A. Swift's electric rifles (TASER; TASER International, Scottsdale, AZ), review the literature, and discuss the management of this complex trauma. DESIGN: Multicenter, retrospective case series and literature review. PARTICIPANTS: Seventeen eyes of 16 patients (5 eyes of 5 patients treated at 3 institutions, and 12 eyes of 11 previously reported cases). METHODS: The clinical data of 17 eyes were pooled. Spearman's correlation coefficient was used to assess the association between the extent of TASER injury and patient outcomes. MAIN OUTCOME MEASURES: Extent of TASER injury (zone of injury, penetrating vs. perforating) and association with patient outcomes (visual acuity [VA] and retinal detachment [RD]). RESULTS: In our cohort, 4 patients were transported by law enforcement and 1 was transferred from a community hospital. Four patients were taken to the operating room for TASER removal and globe repair; 1 patient underwent removal in the emergency room. Of 17 pooled cases, 12 (71%) involved open-globe injury. Of these, there was a high rate of zone 3 injuries (100%; n = 12) and a high incidence of RD (73%; 8 of 11, eviscerated eye excluded). Among patients with closed-globe injury (n = 5), 1 patient demonstrated exudative RD and 1 patient demonstrated retinal dialysis with RD. Of 10 patients with RD, 1 (10%) achieved resolution with monitoring (exudative RD); 1 (10%) underwent cryopexy and pneumatic retinopexy; 3 (30%) underwent vitrectomy, and 5 (50%) with poor prognosis did not undergo vitreoretinal surgery. In the 3 patients who underwent vitrectomy, all 3 (100%) demonstrated redetachment resulting from proliferative vitreoretinopathy and required additional surgery. Visual acuity on presentation was significantly correlated with final VA (ρ = 0.783; P = 0.02). Men (94%) were more likely than women (6%) to sustain TASER trauma. Median age was 26 years. There was a 50% rate of loss to follow-up. CONCLUSIONS: Thomas A. Swift's electric rifle injuries to the eyes or ocular adnexa represent complex trauma. Zone 3 injuries are common. The visual prognosis is guarded, and eyes may require multiple surgeries to preserve vision. Patients are at high risk for loss to follow-up by way of incarceration.

Remodeling of Rectal Innervation After Pullthrough Surgery for Hirschsprung Disease: Relevance to Criteria for the Determination of Retained Transition Zone.

BACKGROUND: After pullthrough surgery for Hirschsprung disease (HSCR), Glut1-positive submucosal nerve hypertrophy is used to diagnose retained transition zone in the neorectum. We hypothesized that pelvic nerves, severed during pullthrough surgery, sprout into the neorectum to mimic transition zone. METHODS: The density (nerves/100x field) and maximum diameter of Glut1-positive submucosal nerves were measured in biopsies and redo resections from 20 patients with post-pullthrough obstructive symptoms. Their original and/or redo resections excluded unequivocal features of transition zone (myenteric hypoganglionosis or partial circumferential aganglionosis) in 17. Postoperative values were compared with control data from 28 cadaveric and 6 surgical non-HSCR specimens, and 14 primary HSCR resections. When possible, nerves were tracked from attached native pelvic soft tissue or aganglionic rectal cuff into the pulled-through colon. RESULTS: Glut1-positive submucosal nerves were not present in the 11 colons of non-HSCR infants less than 1 year of age, except sparsely in the rectum. In 17 older non-HSCR controls, occasional Glut1-positive nerves were observed in prerectal colon and were larger and more numerous in the rectum. In redo resections, Glut1-positive submucosal innervation in post-pullthrough specimens did not differ significantly from age-appropriate non-HSCR rectal controls and pelvic Glut1-positive nerves were never observed to penetrate the pulled-through colon. However, the density and caliber of Glut1-positive nerves in the neorectums were significantly greater than expected based on the prerectal location from which the pulled-through bowel originated. CONCLUSIONS: Submucosal innervation in post-pullthrough specimens does not support the hypothesis that native pelvic nerves innervate the neorectum, but suggests remodeling occurs to establish the age-appropriate density and caliber of rectal Glut1-positive innervation. The latter should not be interpreted as transition zone pullthrough in a rectal biopsy from a previously done pullthrough.

Human papillomavirus infection mediates response and outcome of vulvar squamous cell carcinomas treated with radiation therapy.

PURPOSE: Human papillomavirus (HPV) is implicated as a causative factor in vulvar squamous cell carcinoma (VSCC). This study evaluates if p16-positivity, a surrogate for HPV, predicts for better response rates to chemoradiation therapy and survival. MATERIALS AND METHODS: We conducted a retrospective chart review of women treated with neoadjuvant or definitive chemoradiation (CRT) therapy from 2000 to 2016 for VSCC. p16 stain-positivity was defined as diffuse strong "block" immunoreactivity within invasive tumor. RESULTS: Seventy-three women with median follow-up of 13.4 months were analyzed. Thirty-three (45.2%) had p16+ tumors. Median age was 73 years (range: 37-89); with p16+ tumors, the median age was 60 years vs 73 years for women with p16- tumors (p < 0.001). The distribution of tumor size and stage by p16-status were similar. The complete clinical response (cCR) rate for p16+ tumors was 63.6% vs 35.0% for p16- tumors (p = 0.014). The pathologic complete response (pCR) rate for women treated neoadjuvantly was 53.8% vs 31.4% for p16+ vs p16-, respectively (p = 0.067). The combined complete response (cCR orpCR [CCR]) rate was 63.6% for p16+ and 30.0% for p16- (p = 0.004). Two-year vulvar control (VC) for women with p16+ tumors was 75.5% vs. 49.5% for p16- (p = 0.008). In women with p16+ tumors who achieved CCR, 2-year VC was 92.3% vs 52.1% for CIR (p = 0.009). For p16- tumors, 2-year VC was 67.3% vs 41.1% for CCR and CIR (p = 0.072). No woman with a p16+ tumor developed distant metastases vs. 7 with p16- tumor (p = 0.013). OS was not statistically different between p16+ cohorts, but was improved for p16- patients with CR vs CIR, 72.9% vs 18.8% (p = 0.026). CONCLUSIONS: p16-positive tumors appear to have better clinical and pathologic response rates and clinical outcomes.

Choroidal infarction following ophthalmic artery chemotherapy.

BACKGROUND: Methylenetetrahydrofolate reductase (MTHFR) genetic mutations and intra-procedural inhaled nitrous oxide (N2O) independently increase blood levels of homocysteine, a compound associated with thrombosis. Patients with MTHFR mutations who also receive N2O during ophthalmic artery chemotherapy (OAC) for retinoblastoma may have a heightened thrombotic risk. CASE PRESENTATIONS: Single-center retrospective review of pediatric patients with advanced retinoblastoma who received OAC and developed choroidal infarcts. Four retinoblastoma patients with advanced intraocular disease (2 males, 2 females: 13-58 months) experienced choroidal infarcts within the one-month period after OAC, in which procedural N2O induction was used (duration between 21 and 58 min). All 4 patients had MTHFR (chromosome 1p, position 36.22) genetic abnormalities: one was homozygous for the C677T mutation, one was C677T heterozygous, one was A1298C heterozygous, and one was heterozygous for both C677T and A1298C. In all 4 patients, indirect ophthalmoscopy and fundus photography showed marked disturbance of the retinal pigment epithelium and optical coherence tomography (OCT) confirmed thinning of the choroid. Follow-up time ranged from 15 to 46 months (median 21 months). CONCLUSIONS: Choroidal infarction in eyes treated with OAC developed in children who were both deficient in at least one working allele of the MTHFR gene (heterozygous or homozygous) and received N2O induction during OAC.

A case series of atypical features of patients with biopsy-proven isolated IgG4-related hypophysitis and normal serum IgG4 levels.

BACKGROUND: IgG4-related hypophysitis is a rare clinical entity that forms part of an emerging group of multi-organ IgG4-related fibrosclerotic systemic diseases. The rare prevalence of the disease, presenting features that overlap with other sellar pathologies, and variable imaging features can make preoperative identification challenging. PURPOSE AND METHODS: We report three cases of isolated IgG4-related hypophysitis with atypical clinical and imaging features that mimicked those of pituitary apoplexy and other sellar lesions. Additionally, we review the literature of IgG4-related hypophysitis to provide context for individual patient data described herein. RESULTS: All patients presented with symptoms that mimicked those of pituitary apoplexy and visual disturbance, and MRI findings suggestive of pituitary macroadenoma, Rathke's cleft cyst and craniopharyngioma. The clinical presentation warranted surgical decompression, resulting in rapid symptomatic improvement. Preoperative high-dose followed by postoperative low-dose glucocorticoid replacement therapy was administered in all cases. Histopathology showed dense infiltrate of IgG4 cells. Post-operative follow-up monitoring for 12-26 months revealed normal serum IgG4 levels with no other organ involvement, while endocrinological testing revealed persistent pituitary hormone deficiencies. CONCLUSIONS: Our cases highlight the importance of considering IgG4-related hypophysitis in the differential diagnosis of solid and cystic sellar lesions presenting acutely with pituitary apoplexy symptoms. Existing diagnostic criteria may not be sufficiently precise to permit rapid and reliable identification, or avoidance of surgery in the acute setting. In contrast to other reports of the natural history of this condition, despite the severity of presenting features, the disease in our cases was pituitary-restricted with normal serum IgG4 levels.

Factors associated with Indigenous youths' abstinence from drinking.

The proportion of youth who abstain from alcohol use decreases during adolescence but little attention has focused on factors associated with abstinence. No research has examined this question for Indigenous youth, many of whom live in communities experiencing high rates of alcohol-related health problems. Using data from a longitudinal study of Indigenous youth (n = 649, ages 10-17 years) in the U.S. and Canada, the current study investigates factors associated promoting or decreasing abstaining from alcohol use. Results from generalized linear growth models demonstrate that abstinence declines significantly during adolescence. In concurrent models, caretaker monitoring and school adjustment increased the odds of abstaining, and frequency of smoking cigarettes and number of best friends who drink decreased the odds. In lagged analysis, only school adjustment, smoking, and peer drinking remained significant. Time-stable characteristics moderated several time-varying associations. This study has important implications for programs aimed at encouraging alcohol abstinence.

The Importance of Titrating Antibodies for Immunocytochemical Methods.

When using immunocytochemistry, investigators may not know how to optimize staining or how to troubleshoot the method when staining fails. Lacking are guides for comparing techniques and applying information derived from one staining method to another. Newer methods amplify signal detection, but will not necessarily work at the same primary antibody concentrations used for less sensitive reactions. Recommendations of optimal titers are often not accurate and are not usually accompanied by information on the method used to test those antibodies or the specifics of the assay. When the staining does not work, the investigators do not know how to determine if the antiserum is bad, the tissue is bad, or the method is inappropriate for their staining. This unit describes detailed procedures for determining optimal staining and applying that information to three common immunofluorescence methods. Lastly, a formula is provided for converting among the different methods. © 2016 by John Wiley & Sons, Inc.

Cicatrizing Conjunctivitis in a Patient Diagnosed With Drug Reaction With Eosinophilia and Systemic Symptoms/Drug-Induced Hypersensitivity Syndrome but With Features of Stevens-Johnson Syndrome.

PURPOSE: Severe cutaneous adverse reactions to drugs (SCARs) such as Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) and drug reaction with eosinophilia and systemic symptoms/drug-induced hypersensitivity syndrome (DRESS/DIHS) serve as one of the main reasons for inpatient ophthalmic consultation. Although it is well-recognized that SJS/TEN is associated with severe ocular mucosal inflammation and cicatrizing, potentially blinding, sequelae, this association has not been described in relation to other SCARs. We present a patient fulfilling the diagnostic criteria for probable DRESS/DIHS but not for SJS/TEN, yet exhibiting the severe ocular surface involvement characteristic of SJS/TEN. METHODS: Case report. RESULTS: A 64-year-old man presented with bilateral pseudomembranous conjunctivitis and conjunctival denudation (sloughing) in the setting of a maculopapular rash, fever, liver dysfunction, and hematologic abnormalities 1 month after initiating several medications. A skin biopsy was not consistent with SJS/TEN. The patient was diagnosed with probable DRESS/DIHS and treated with high-dose systemic corticosteroids. The ocular surface inflammation was addressed with intensive topical corticosteroid ointment. The pseudomembranes resolved over a 6-week period, but the patient exhibited residual conjunctival scarring of all palpebral surfaces. CONCLUSIONS: The development of severe ocular surface mucosal inflammation and denudation with cicatrizing sequelae in a patient carrying a diagnosis of DRESS/DIHS has diagnostic and therapeutic implications for the ophthalmologist. Careful ophthalmic assessment is indicated in any SCAR patient with ophthalmic symptoms, regardless of formal diagnosis. Furthermore, the early therapeutic interventions recently recommended in SJS/TEN to limit the ophthalmic cicatricial sequelae, such as systemic or topical corticosteroids, may be indicated.

Survival advantage associated with multimodal therapy in women with node-positive (stage-IIIC) uterine papillary serous carcinoma: a National Cancer Database study.

OBJECTIVE: Uterine papillary serous carcinoma (UPSC) is an aggressive subtype of endometrial cancer. Adjuvant chemotherapy (CT) has become standard care in treatment of women with advanced-stage UPSC, but the role of consolidative radiotherapy (RT) is unclear. This study aims to evaluate survival outcomes of multimodal therapy. DESIGN: Retrospective cohort study using a National Cancer Database (NCDB). SETTING: United States of America. SAMPLE: A total of 1816 women diagnosed with UPSC. METHODS: All women diagnosed with surgically staged FIGO (International Federation of Gynecology and Obstetrics) stage-IIIC UPSC were identified in the NCDB from January 1998 to December 2010. Overall survival (OS) was estimated using the Kaplan-Meier method. Univariate and multivariable analyses were performed to identify and control for prognostic factors. MAIN OUTCOME MEASURE: Overall survival. RESULTS: A total of 398 057 cases of uterine cancer were identified, 22 106 of which were UPSC. Of these women, 14 093 underwent lymph-node examination, 2902 (20.6%) were found to have stage-IIIC disease, and 1816 received chemotherapy. Younger age and higher number of total lymph nodes examined were independently predictive of receiving multimodality (CT + RT) therapy, compared with CT only. Median OS was 33.6 and 42.6 months, for the CT and CT + RT groups, respectively (P < 0.0005). Exploratory univariate analyses found age, comorbidity index, tumour size, and number of dissected and positive lymph nodes to be also associated with survival. Multivariable analysis controlling for the above found the use of consolidative radiotherapy to be independently predictive of improved OS, with a hazard ratio of 0.69 (95% confidence interval, 95% CI 0.56-0.84). CONCLUSIONS: Patients with stage-IIIC UPSC may benefit from multimodal treatment that includes adjuvant radiotherapy in addition to chemotherapy. TWEETABLE ABSTRACT: In this study of 1816 women with uterine papillary serous cancer, adjuvant radiotherapy increased survival.

Impact of a Drop-in Group Medical Appointment on Tobacco Quit Rates.

The tobacco quit rate of veterans on pharmacotherapy who attended at least 1 drop-in group session was higher than the quit rate of veterans only on pharmacotherapy.

Alternating Hemiplegia of Childhood: Retrospective Genetic Study and Genotype-Phenotype Correlations in 187 Subjects from the US AHCF Registry.

Mutations in ATP1A3 cause Alternating Hemiplegia of Childhood (AHC) by disrupting function of the neuronal Na+/K+ ATPase. Published studies to date indicate 2 recurrent mutations, D801N and E815K, and a more severe phenotype in the E815K cohort. We performed mutation analysis and retrospective genotype-phenotype correlations in all eligible patients with AHC enrolled in the US AHC Foundation registry from 1997-2012. Clinical data were abstracted from standardized caregivers' questionnaires and medical records and confirmed by expert clinicians. We identified ATP1A3 mutations by Sanger and whole genome sequencing, and compared phenotypes within and between 4 groups of subjects, those with D801N, E815K, other ATP1A3 or no ATP1A3 mutations. We identified heterozygous ATP1A3 mutations in 154 of 187 (82%) AHC patients. Of 34 unique mutations, 31 (91%) are missense, and 16 (47%) had not been previously reported. Concordant with prior studies, more than 2/3 of all mutations are clusteredin exons 17 and 18. Of 143 simplex occurrences, 58 had D801N (40%), 38 had E815K(26%) and 11 had G947R (8%) mutations [corrected].Patients with an E815K mutation demonstrate an earlier age of onset, more severe motor impairment and a higher prevalence of status epilepticus. This study further expands the number and spectrum of ATP1A3 mutations associated with AHC and confirms a more deleterious effect of the E815K mutation on selected neurologic outcomes. However, the complexity of the disorder and the extensive phenotypic variability among subgroups merits caution and emphasizes the need for further studies.