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1.
J AAPOS ; 2019 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-31678481

RESUMO

Most cases of strabismus have a chronic and stable or known etiologic diagnosis prior to surgery. In some cases, however, surgery is undertaken to correct a stable ocular misalignment without a definitive etiology. We present 2 cases, one with euthyroid Graves' orbitopathy and the other with amyloid light-chain amyloidosis, in which extraocular muscle biopsy performed intraoperatively allowed histopathologic confirmation of a clinical diagnosis.

2.
Hum Vaccin Immunother ; : 1-8, 2019 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-31689166

RESUMO

In randomized active-comparator controlled studies, DTaP5-HB-IPV-Hib showed comparable immunogenicity and safety to other licensed vaccines. This study assessed persistence of anti-hepatitis B surface antigen (HBs) and anti-pertussis antibodies, when children were 4 to 5 years of age, 3 to 4 years after initial infant/toddler hexavalent vaccination. This was an extension of 2 European studies in which infants/toddlers received either DTaP5-HB-IPV-Hib or DTaP3-HB-IPV/Hib on a 2 + 1 or 3 + 1 schedule. Primary endpoints included percentages with anti-HBs ≥10 mIU/mL, and anti-pertussis toxin (PT), anti-filamentous hemagglutinin (FHA), anti-pertactin (PRN), and anti-fimbriae types 2 & 3 (FIM) greater than or equal to the lower limit of quantitation (LLOQ). One month after 2 + 1 or 3 + 1 dosing, nearly all toddlers had anti-HBs ≥10 mIU/mL, and responded to the received pertussis antigens. Approximately 3 to 4 years later, 65.8%-70.2% in the DTaP5-HB-IPV-Hib and 82.0%-83.7% in the DTaP3-HB-IPV/Hib groups, respectively, had anti-HBs ≥10 mIU/mL. Percentages of children with pertussis antibodies above LLOQ after 2 + 1 dosing were 58.4% and 41.5% (anti-PT), 80.9% and 88.3% (anti-FHA), 66.1% and 72.6% (anti-PRN), and 94.4% and 3.3% (anti-FIM), in the DTaP5-HB-IPV-Hib and DTaP3-HB-IPV/Hib groups, respectively. This study demonstrated, as expected, waning of hepatitis B and pertussis antibodies during the 3 to 4 years after completion of a 3 + 1 or 2 + 1 hexavalent vaccination schedule. Nonetheless, anti-HBs levels ≥10 IU/mL and detectable antibodies against acellular pertussis antigens persisted in most study participants. The implications of these findings for the long-term prevention of hepatitis B and pertussis are further discussed.

3.
Artigo em Inglês | MEDLINE | ID: mdl-31675433

RESUMO

Insulin resistance increases renal oxidant production by up-regulating NADPH oxidase 4 (Nox4) expression contributing to oxidative damage and ultimately albuminuria. Inhibition of the renin-angiotensin system (RAS) and activation of glucagon-like peptide-1 (GLP-1) receptor signaling may reverse this effect. However, whether angiotensin receptor type 1 (AT1) blockade and GLP-1 receptor activation improve oxidative damage and albuminuria through different mechanisms is not known. Using insulin resistant Otsuka Long Evan Tokushima Fatty (OLETF) rats, we tested the hypothesis that simultaneous blockade of AT1 and activation of GLP-1r additively decrease oxidative damage and urinary albumin excretion (Ualb V) in the following groups: (1) untreated, lean LETO (n=7), (2) untreated, obese OLETF (n=9), (3) OLETF + angiotensin receptor blocker (ARB; 10 mg olmesartan /kg/d; n=9), (4) OLETF + GLP-1 mimetic (EXE; 10 ug exenatide/kg/d; n=7), and (5) OLETF + ARB + exenatide (Combo; n=6). Mean kidney Nox4 protein expression and nitrotyrosine (NT) levels were 30% and 46% greater, respectively, in OLETF compared to LETO. Conversely, Nox4 protein expression and NT were reduced to LETO levels in ARB and EXE, and Combo reduced Nox4, NT, and 4-hydroxy-2-nonenal levels by 21%, 27%, and 27%, respectively. At baseline, Ualb V was nearly double in OLETF compared to LETO, and increased to nearly 10-fold greater levels by the end of the study. While ARB (45%) and EXE (55%) individually reduced Ualb V, the combination completely ameliorated the albuminuria. Collectively, these data suggest that AT1 blockade and GLP-1 receptor activation reduce renal oxidative damage similarly during insulin resistance, while targeting both signaling pathways provides added benefit in restoring and/or further ameliorating albuminuria in a model of diet-induced obesity.

4.
Sci Immunol ; 4(41)2019 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-31704735

RESUMO

Although immune checkpoint blockade therapies have demonstrated clinical efficacy in cancer treatment, harnessing this strategy is largely encumbered by resistance in multiple cancer settings. Here, we show that tumor-infiltrating T cells are severely exhausted in the microsatellite stable (MSS) colorectal cancer (CRC), a representative example of PD-1 blockade-resistant tumors. In MSS CRC, we found wound healing signature to be up-regulated and that T cell exhaustion is driven by vascular endothelial growth factor-A (VEGF-A). We report that VEGF-A induces the expression of transcription factor TOX in T cells to drive exhaustion-specific transcription program in T cells. Using a combination of in vitro, ex vivo, and in vivo mouse studies, we demonstrate that combined blockade of PD-1 and VEGF-A restores the antitumor functions of T cells, resulting in better control of MSS CRC tumors.

5.
J Phys Chem B ; 2019 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-31696711

RESUMO

Isotope substitution of enzymes has become a means of addressing the participation of protein motions in enzyme-catalyzed reactions. The idea is that only the enzyme mass will be altered and not the electrostatics, so that the protein dynamics are essentially the same but at lower frequencies due to the mass change. In this study, we variably label all carbon atoms in formate dehydrogenase with 13C, all nitrogen atoms with 15N, and all non-exchangeable hydrogen atoms with deuterium and investigate the impact that isotopic substitution has on the dynamics at the active site by 2D IR spectroscopy and compare to measurements of the temperature dependence of the intrinsic KIEs. We show that 15N labeling of FDH has the largest effect and makes the active site more heterogeneous, while the addition of non-exchangeable deuterium appears to have the opposite effect of 15N on active site dynamics, resulting in behavior similar to the native FDH. Nevertheless, the temperature dependence of the KIE shows a monotonic trend with protein mass that does not correspond with the changes in dynamics. These results suggest that isotope labeling has more than just a mass effect on enzyme dynamics and may influence electrostatics in ways that complicate the interpretation of the protein isotope effect.

6.
Ann Surg Oncol ; 2019 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-31659645

RESUMO

BACKGROUND: Anastomotic failure (AF) after cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) remains a dreaded complication. Whether specific factors, including anastomotic technique, are associated with AF is poorly understood. METHODS: Patients who underwent CRS-HIPEC including at least one bowel resection between 2000 and 2017 from 12 academic institutions were reviewed to determine factors associated with AF (anastomotic leak or enteric fistula). RESULTS: Among 1020 patients who met the inclusion criteria, the median age was 55 years, 43.9% were male, and the most common histology was appendiceal neoplasm (62.3%). The median Peritoneal Cancer Index was 14, and 93.2% of the patients underwent CC0/1 resection. Overall, 82 of the patients (8%) experienced an AF, whereas 938 (92.0%) did not. In the multivariable analysis, the factors associated with AF included male gender (odds ratio [OR], 2.2; p < 0.01), left-sided colorectal resection (OR 10.0; p = 0.03), and preoperative albumin (OR 1.8 per g/dL; p = 0.02).Technical factors such as method (stapled vs hand-sewn), timing of anastomosis, and chemotherapy regimen used were not associated with AF (all p > 0.05). Anastomotic failure was associated with longer hospital stay (23 vs 10 days; p < 0.01), higher complication rate (90% vs 59%; p < 0.01), higher reoperation rate (41% vs 9%; p < 0.01), more 30-day readmissions (59% vs 22%; p < 0.01), greater 30-day mortality (9% vs 1%; p < 0.01), and greater 90-day mortality (16% vs 8%; p = 0.02) as well as shorter median overall survival (25.6 vs 66.0 months; p < 0.01). CONCLUSIONS: Among patients undergoing CRS-HIPEC, AF is independently associated with postoperative morbidity and worse long-term outcomes. Because patient- and tumor-related, but not technical, factors are associated with AF, operative technique may be individualized based on patient considerations and surgeon preference.

7.
J Neuroophthalmol ; 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31633590

RESUMO

BACKGROUND: Spaceflight-associated neuro-ocular syndrome (SANS) was first described in 2011 and is associated with structural ocular changes found to occur in astronauts after long-duration missions. Despite multiple insufficient potential terrestrial models, an understanding of the etiology has yet to be described. EVIDENCE ACQUISITION: A systematic review was conducted on literature published about the pathophysiology of cerebral edema. Databases searched include PubMed, Scopus, and the Texas Medical Center Online Library. This information was then applied to create theories on mechanisms on SANS etiology. RESULTS: Cerebral edema occurs through 2 general mechanisms: redistribution of ions and water intracellularly and displacement of ions and water from the vascular compartment to the brain parenchyma. These processes occur through interconnected endocrine and inflammatory pathways and involve mediators such as cytokines, matrix metalloproteases, nitric oxide, and free radicals. The pathways ultimately lead to a violation of cellular membrane ionic gradients and blood-brain barrier degradation. By applying the principles of cerebral edema pathophysiology to the optic disc edema (ODE) see in SANS, several theories regarding its etiology can be formed. Venous stasis may lead to ODE through venous and capillary distension and leak, as well as relative hypoxia and insufficient ATP substrate delivery causing axoplasmic flow stasis and local oxidative stress. CONCLUSIONS: Using the pathophysiology of cerebral edema as a model, hypotheses can be inferred as to the etiology of ODE in SANS. Further studies are needed to determine the presence and contribution of local vascular stasis and resulting inflammation and oxidative stress to the pathophysiology of SANS.

8.
J Neuroophthalmol ; 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31633591

RESUMO

Giant cell arteritis (GCA) is a medium-to-large vessel vasculitis of the elderly. Common constitutional clinical features include headache, scalp tenderness, and jaw claudication. Severe unilateral or bilateral visual loss is the most feared ophthalmic complication of GCA. Scalp necrosis is a known ischemic complication of GCA with approximately 100 cases reported in the literature to date. We report a case of scalp pain and an erythematous cutaneous lesion in the distribution of ophthalmic division of the trigeminal nerve that mimicked herpes zoster ophthalmicus. A temporal artery biopsy was positive for GCA, and small vessel arteritis was seen at the time of simultaneous skin biopsy. To the best of our knowledge, this is the first such report in the English language ophthalmic literature.

11.
Ann Surg Oncol ; 2019 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-31602579

RESUMO

BACKGROUND: For patients with peritoneal carcinomatosis undergoing cytoreductive surgery with heated intraperitoneal chemotherapy (CRS/HIPEC), incomplete cytoreduction (CCR2/3) confers morbidity without survival benefit. The aim of this study is to identify preoperative factors which predict CCR2/3. METHODS: All patients who underwent curative-intent CRS/HIPEC of low/high-grade appendiceal, colorectal, or peritoneal mesothelioma cancers in the 12-institution US HIPEC Collaborative from 2000 to 2017 were included (n = 2027). The primary aim is to create an incomplete-cytoreduction risk score (ICRS) to predict CCR2/3 CRS utilizing preoperative data. ICRS was created from a randomly selected cohort of 50% of patients (derivation cohort) and verified on the remaining patients (validation cohort). RESULTS: Within our derivation cohort (n = 998), histology was low-grade appendiceal neoplasms in 30%, high-grade appendiceal tumor in 41%, colorectal tumor in 22%, and peritoneal mesothelioma in 8%. CCR0/1 was achieved in 816 patients and CCR 2/3 in 116 patients. On multivariable analysis, preoperative factors associated with incomplete cytoreduction were male gender [odds ratio (OR) 3.4, p = 0.007], presence of ascites (OR 2.8, p = 0.028), cancer antigen (CA)-125 ≥ 40 U/mL (OR 3.4, p = 0.012), and carcinoembryonic antigen (CEA) ≥ 4.2 ng/mL (OR 3.2, p = 0.029). Each preoperative factor was assigned a score of 0 or 1 to form an ICRS from 0 to 4. Scores were grouped as zero (0), low (1-2), or high (3-4). Incidence of CCR2/3 progressively increased by risk group from 1.6% in zero to 13% in low and 39% in high. When ICRS was applied to the validation cohort (n = 1029), this relationship was maintained. CONCLUSION: The incomplete cytoreduction risk score incorporates preoperative factors to accurately stratify the risk of CCR2/3 resection in CRS/HIPEC. This score should not be used in isolation, however, to exclude patients from surgery.

12.
Curr Opin Ophthalmol ; 30(6): 462-466, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31567467

RESUMO

PURPOSE OF REVIEW: This article will update and review the Miller Fisher variants (MFV) of Guillain-Barré syndrome (GBS) including the clinical presentation, diagnostic testing, and treatment. RECENT FINDINGS: Although the diagnosis of GBS and MFV can be made on clinical grounds, cerebrospinal fluid (CSF) analysis, nerve conduction studies, imaging (e.g. ultrasound and MRI), and serologic testing can help to confirm the diagnosis. Some patients may need immunotherapy with either intravenous immunoglobulin (IVIg) or plasma exchange, and recent studies suggest that complement inhibition combined with IVIg could be of benefit, but further studies are needed to prove efficacy. SUMMARY: GBS is characterized by an acute, ascending polyneuropathy, ataxia, areflexia, and CSF albuminocytologic dissociation. The MFV of GBS is associated with ophthalmoplegia. Clinicians should have high index of suspicion for MFV of GBS in patients with acute ophthalmoplegia in order to establish the diagnosis, perform appropriate evaluation, and start treatment. SDC VIDEO LINK:.

14.
Can J Ophthalmol ; 54(5): e241-e244, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31564366
16.
Laryngoscope ; 2019 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-31566748

RESUMO

OBJECTIVES: Postoperative hemorrhage is a serious complication of tonsillectomy, with secondary bleeding rates affecting up to 0.8% to 3% of patients. Although these bleeds are anecdotally perceived as occurring more frequently at night, the occurrence of hemorrhage relative to the time of day has not been investigated. We measured the frequency of post-tonsillectomy hemorrhage onset relative to the time of day. METHODS: We reviewed electronic medical records of all patients who experienced postprocedural hemorrhage (International Classification of Disease, Ninth Edition [ICD-9] 998.11, ICD-10 J95.830 at two hospitals within a tertiary academic health system in a 10-year period). Patient demographics, time of bleed onset, emergency room [ED] arrival time, and management (operating room vs. observation) were abstracted. Patients without a recorded bleeding time were excluded. Time of bleed onset was categorized as morning (6:01 am-12 pm), afternoon (12:01 pm-6 pm), evening (6:01 pm-12 am), or overnight (12:01 am-6 am). Chi-square goodness of fit test was used to assess the distribution of hemorrhage timing (P ≤ 0.05). RESULTS: A total of 7,396 patients underwent tonsillectomy May 2008 through May 2018, among whom 121 (2%) post-tonsillectomy hemorrhage patients were identified. Among the 104 patients with ED arrival times, 29 (28%) arrived in the morning; 15 (14%) arrived in the afternoon; 40 (38%) arrived in the evening; and 20 (19%) arrived overnight (P = 0.003). Sixty patients (mean age 17.1 years, standard deviation 16.6) had a recorded timing of bleed onset. Bleed onset occurred most commonly overnight (24, 40%), followed by evening (21, 35%), afternoon (11, 18%), and morning (4, 7%) (P = 0.0007). CONCLUSION: In this cohort, post-tonsillectomy hemorrhage occurred most frequently between midnight and 6 am. Our findings confirm anecdotal experience and provide data in setting caregiver expectations. LEVEL OF EVIDENCE: 4 Laryngoscope, 2019.

17.
Eye (Lond) ; 2019 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-31570813

RESUMO

BACKGROUND: Vertebrobasilar insufficiency (VBI) after rotation or hyperextension of the neck during otherwise routine activities is uncommon "hairdresser syndrome" (HDS). We report three such cases presenting with neuro-ophthalmic complaints (Horner syndrome, ophthalmoplegia, and transient vision loss). METHODS: A retrospective review was performed of the electronic health records of three patients seen in the neuro-ophthalmology clinic of Houston Methodist Hospital with acute neuro-ophthalmological signs after neck hyperextension. A literature review was also performed. RESULTS: While various ischemic signs of VBI have been previously documented, to our knowledge, these are the first cases in the English ophthalmic literature to describe the presenting neuro-ophthalmologic signs of HDS. CONCLUSION: Clinicians should consider the possibility of neck hyperextension as a potential mechanism and precipitating event for acute neuro-ophthalmic presentations of VBI. Patients with a history of occupational (e.g., carpenter), recreational (e.g., bow hunter), or cosmetic (hairdresser) neck hyperextension (i.e., possible HDS) should undergo structural and vascular neuroimaging of both the head and neck (e.g., CT/CTA or MRI/MRA) to look for evidence of posterior fossa ischemia and/or vertebrobasilar lesion (e.g., occlusion, dissection, FMD, and pseudoaneurysm).

19.
Environ Sci Technol ; 53(21): 12366-12378, 2019 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-31490675

RESUMO

Glass transitions of secondary organic aerosols (SOA) from liquid/semisolid to solid phase states have important implications for aerosol reactivity, growth, and cloud formation properties. In the present study, glass transition temperatures (Tg) of isoprene SOA components, including isoprene hydroxy hydroperoxide (ISOPOOH), isoprene-derived epoxydiols (IEPOX), 2-methyltetrols, and 2-methyltetrol sulfates, were measured at atmospherically relevant cooling rates (2-10 K/min) by thin film broadband dielectric spectroscopy. The results indicate that 2-methyltetrol sulfates have the highest glass transition temperature, while ISOPOOH has the lowest glass transition temperature. By varying the cooling rate of the same compound from 2 to 10 K/min, the Tg of these compounds increased by 4-5 K. This temperature difference leads to a height difference of 400-800 m in the atmosphere for the corresponding updraft induced cooling rates, assuming a hygroscopicity value (κ) of 0.1 and relative humidity less than 95%. The Tg of the organic compounds was found to be strongly correlated with volatility, and a semiempirical formula between glass transition temperatures and volatility was derived. The Gordon-Taylor equation was applied to calculate the effect of relative humidity (RH) and water content at five mixing ratios on the Tg of organic aerosols. The model shows that Tg could drop by 15-40 K as the RH changes from <5 to 90%, whereas the mixing ratio of water in the particle increases from 0 to 0.5. These results underscore the importance of chemical composition, updraft rates, and water content (RH) in determining the phase states and hygroscopic properties of organic particles.

20.
J Neuroophthalmol ; 2019 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-31524841

RESUMO

A 67-year-old woman presented with acute loss of vision to no light perception (NLP), a right afferent pupillary defect, and anisocoria with a nonreactive and dilated pupil in the right eye. Fundus examination showed pallid optic disc edema and a central retinal artery occlusion (CRAO) in the right eye. A temporal artery biopsy showed giant cell arteritis (GCA). Orbital involvement in GCA has been reported previously. However the combination of an afferent and efferent pupillary defect, NLP vision, pallid disc edema, and a CRAO in an elderly patient is likely a unique clinical combination that should strongly suggest GCA. Clinicians should be aware of the myriad presentations of GCA, including orbital ischemia.

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