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ABSTRACT: Cutaneous melanoma can lead to metastasis, and it is associated with high mortality. Currently, there are no widely accepted immunohistochemistry markers for melanoma prognosis in routine staging. Preferentially expressed antigen in melanoma (PRAME) is a possible biomarker for prognosis in several noncutaneous neoplasms. Ki-67 is a cell proliferation marker correlated with poor outcomes in many cancers. This study assessed PRAME and Ki-67 as potential prognostic markers for sentinel lymph node outcomes and survival among melanoma patients. This is a retrospective study analyzing cutaneous melanoma cases from a Brazilian cancer center (2005-2021). All cases were tested using immunohistochemistry to evaluate PRAME expression and Ki-67 index. Descriptive analysis, Spearman correlations, means comparison, Kaplan-Meier analysis, χ2, and Cox models were performed. In univariate analysis of 123 cutaneous melanoma cases, high extent (P = 0.0267) and elevated intensity (P = 0.043) of PRAME were associated with decreased overall survival. The Ki-67 index was associated with overall survival (P = 0.05) and sentinel lymph node status (P = 0.0403), with a positive correlation between the markers (P = 0.0004) and between Ki-67 and Breslow thickness (P = 0.0001). However, in multivariate analysis, only Breslow thickness significantly influenced overall survival (P = 0.0003). Then, the present results can suggest that elevated PRAME and Ki-67 expression are associated with poor overall survival in cutaneous melanoma; however, in multivariate analysis, only the Breslow thickness had a significant influence. These findings highlight the potential of PRAME and Ki-67 as prognostic markers, opening frontiers that could improve strategies for treating cutaneous melanoma.

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The development of specific, safe, and potent monoclonal antibodies (Abs) has led to novel therapeutic options for infectious disease. In addition to preventing viral infection through neutralization, Abs can clear infected cells and induce immunomodulatory functions through engagement of their crystallizable fragment (Fc) with complement proteins and Fc receptors on immune cells. Little is known about the role of Fc effector functions of neutralizing Abs in the context of encephalitic alphavirus infection. To determine the role of Fc effector function in therapeutic efficacy against Venezuelan equine encephalitis virus (VEEV), we compared the potently neutralizing anti-VEEV human IgG F5 (hF5) Ab with intact Fc function (hF5-WT) or containing the loss of function Fc mutations L234A and L235A (hF5-LALA) in the context of VEEV infection. We observed significantly reduced binding to complement and Fc receptors, as well as differential in vitro kinetics of Fc-mediated cytotoxicity for hF5-LALA compared to hF5-WT. The in vivo efficacy of hF5-LALA was comparable to hF5-WT at -24 and + 24 h post infection, with both Abs providing high levels of protection. However, when hF5-WT and hF5-LALA were administered + 48 h post infection, there was a significant decrease in the therapeutic efficacy of hF5-LALA. Together these results demonstrate that optimal therapeutic Ab treatment of VEEV, and possibly other encephalitic alphaviruses, requires neutralization paired with engagement of immune effectors via the Fc region.

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BACKGROUND: Most patients who sustain a traumatic injury require outpatient follow-up. A common barrier to outpatient postadmission care is patient failure to follow-up. One of the most significant factors resulting in failure to follow-up is age more than 35 years. Recent work has shown that follow-up telephone calls reduce readmission rates. Our aim was to decrease no-show appointments by 10% in 12 months. STUDY DESIGN: The electronic medical records at our level I and II trauma centers were queried for all outpatient appointments for trauma between July 1, 2020, and June 9, 2021, and whether the patient attended their follow-up appointment. Patients with visits scheduled after August 1, 2021, received 24- and 48-hour previsit reminder calls. Patients with visits scheduled between July 1, 2020, and August 1, 2021, did not receive previsit calls. Both groups were compared using multivariable direct logistic regression models. RESULTS: A total of 1,822 follow-up opportunities were included in the study. During the pre-implementation phase, there was a no-show rate of 30.9% (329 of 1,064 visits). Postintervention, a 12.2% reduction in overall no-show rate occurred. A statistically significant 11.2% decrease (p < 0.001) was seen in elderly patients. Multivariate analysis showed standardized calls resulted in significantly decreased odds of failing to keep an appointment (adjusted odds ratio = 0.610, p < 0.001). CONCLUSIONS: Reminder calls led to a 12.2% reduction in no-show rate and were an independent predictor of a patient's likelihood of attending their appointment. Other predictors of attendance included insurance status and abdominal injury.

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We synthesized the mesoionic compound 2-(4-chlorophenyl)-3-methyl-4-(4-methylphenyl)-1,3-thiazole-5-thiolate and measured its refractive and absorptive nonlinear optical response in different temporal and spectral regimes. The experiments were performed by using the Z-scan technique with two pulsed light sources: the second harmonic (at 532 nm) of a mode-locked and Q-switched Nd-YAG laser (100 ps, 10 Hz) and a Ti: Sapphire laser system (100 fs, 1 kHz) operating at 800 nm. The observation and characterization of nonlinear refraction, two- and three-photon absorption, and excited state absorption of the mesoionic compound dissolved in dimethyl sulfoxide, in different concentrations, are presented and discussed with basis on the population redistribution in a three-energy-level model that allows the determination of the parameters which characterize the nonlinear response.

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BACKGROUND: Nationally, the volume of geriatric falls with intracranial hemorrhage is increasing. Our institution began observing patients with intracranial hemorrhage, Glasgow Coma Scale of 14 or greater, and no midline shift or intraventricular hemorrhage with hourly neurologic examinations outside of the ICU in a high observation trauma (HOT) protocol. We first excluded patients on anticoagulants or antiplatelets (HOT I), then included antiplatelets and warfarin (HOT II), and finally, included direct oral anticoagulants (HOT III). Our hypothesis is that HOT protocol safely reduces ICU use and creates cost savings in this patient population. STUDY DESIGN: Our institutional trauma registry was retrospectively queried for all patients on HOT protocol. Patients were stratified based on date of admission (HOT I [2008-2014], HOT II [2015-2018], and HOT III [2019-2021]), and were compared for demographics, anticoagulant use, injury characteristics, lengths of stay, incidence of neurointervention, and mortality. RESULTS: During the study period, 2,343 patients were admitted: 939 stratified to HOT I, 794 to HOT II, and 610 to HOT III. Of these patients, 331 (35%), 554 (70%), and 495 (81%) were admitted to the floor under HOT protocol, respectively. HOT protocol patients required neurointervention in 3.0%, 0.5%, and 0.4% of cases in HOT I, II, and III, respectively. Mortality among HOT protocol patients was found to be 0.6% in HOT I, 0.9% in HOT II, and 0.2% in the HOT III cohort (p = 0.33). CONCLUSIONS: Throughout the study period ICU use decreased without an increase in neurosurgical intervention or mortality, indicating the efficacy of the HOT selection criteria in identifying appropriate candidates for stepdown admission and HOT protocol.

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OBJECTIVE: The aim of this study was to identify a mortality benefit with the use of whole blood (WB) as part of the resuscitation of bleeding trauma patients. BACKGROUND: Blood component therapy (BCT) is the current standard for resuscitating trauma patients, with WB emerging as the blood product of choice. We hypothesized that the use of WB versus BCT alone would result in decreased mortality. METHODS: We performed a 14-center, prospective observational study of trauma patients who received WB versus BCT during their resuscitation. We applied a generalized linear mixed-effects model with a random effect and controlled for age, sex, mechanism of injury (MOI), and injury severity score. All patients who received blood as part of their initial resuscitation were included. Primary outcome was mortality and secondary outcomes included acute kidney injury, deep vein thrombosis/pulmonary embolism, pulmonary complications, and bleeding complications. RESULTS: A total of 1623 [WB: 1180 (74%), BCT: 443(27%)] patients who sustained penetrating (53%) or blunt (47%) injury were included. Patients who received WB had a higher shock index (0.98 vs 0.83), more comorbidities, and more blunt MOI (all P <0.05). After controlling for center, age, sex, MOI, and injury severity score, we found no differences in the rates of acute kidney injury, deep vein thrombosis/pulmonary embolism or pulmonary complications. WB patients were 9% less likely to experience bleeding complications and were 48% less likely to die than BCT patients ( P <0.0001). CONCLUSIONS: Compared with BCT, the use of WB was associated with a 48% reduction in mortality in trauma patients. Our study supports the use of WB use in the resuscitation of trauma patients.

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OBJECTIVE: To estimate the burden of anemia attributable to malaria, inflammation, and deficiency of iron or vitamin A during low and high malaria seasons among Zambian children. STUDY DESIGN: From a cohort of children (n = 820), 4-8 years of age participating in a randomized controlled trial of pro-vitamin A, we estimated attributable fractions for anemia (hemoglobin of <110 or 115 g/L, by age) owing to current malaria or inflammation (C-reactive protein of >5 mg/L, or α-1 acid glycoprotein of >1 g/L, or both), and current or prior iron deficiency (ID; defined as low ferritin [<12 or 15 µg/L for age <5 or >5 years] or functional ID [soluble transferrin receptor of >8.3 mg/L] or both) and vitamin A deficiency (retinol of <0.7 µmol/L), during low and high malaria seasons, using multivariate logistic regression. Serum ferritin, soluble transferrin receptor, and retinol were adjusted for inflammation. RESULTS: The burden of anemia independently associated with current malaria, inflammation, ID, and vitamin A deficiency in the low malaria season were 12% (P < .001), 6% (P = .005), 14% (P = .001), and 2% (P = .07), respectively, and 32% (P < .001), 15% (P < .001), 10% (P = .06), and 2% (P = .06), respectively, in the high malaria season. In both seasons, functional ID was independently associated with more anemia (approximately 11%) than low ferritin (approximately 4%). Anemia and ID in the low malaria season, accounted for 20% (P < .001) and 4% (P = .095) of the anemia in the subsequent high malaria season. CONCLUSIONS: Anemia in this population is strongly linked to malaria, inflammation, and functional ID, and to a lesser extent, low iron stores. Integrated control strategies are needed.

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OBJECTIVES: To evaluate the optimal zinc supplementation strategy for improving growth and hematologic and micronutrient status in young Laotian children. STUDY DESIGN: In total, 3407 children aged 6-23 months were randomized to receive either daily preventive zinc tablets (7 mg/d), high-zinc, low-iron micronutrient powder (10 mg/d zinc, 6 mg/d iron, and 13 other micronutrients), therapeutic zinc supplementation for diarrhea (20 mg/d for 10 days per episode), or daily placebo powder; all were followed for ~9 months. Anthropometry, hemoglobin, zinc, and iron status were assessed at baseline and endline. Analyses were by intention-to-treat, using linear and modified Poisson regression. RESULTS: At baseline, mean (±SD) age was 14.2 ± 5.1 months and stunting and anemia prevalence were 37.9% and 55.6%, respectively. At endline, zinc deficiency in the preventive zinc (50.7%) and micronutrient powder (59.1%) groups were significantly lower than in the therapeutic zinc (79.2%) and control groups (78.6%; P < .001), with no impact on stunting (37.1%-41.3% across the groups, P = .37). The micronutrient powder reduced iron deficiency by 44%-55% compared with other groups (P < .001), with no overall impact on anemia (P = .14). Micronutrient powder tended to reduce anemia by 11%-16% among children who were anemic at baseline (P = .06). CONCLUSIONS: Despite improving zinc status, preventive zinc and micronutrient powder had no impact on growth. The micronutrient powder improved iron status and tended to reduce anemia among the subset of previously anemic children. TRIAL REGISTRATION: ClinicalTrials.govNCT02428647.

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OBJECTIVE: To assess the cytotoxic activities of crude extracts and solvent fractions of Spermacoce verticillata, Ficus pumila and Flemingia strobilifera against a MT-4 human leukaemia cancer cell line. METHODS: Crude extracts of dried leaves of S verticillata, F pumila and F strobilifera were made by exhaustive methanol extraction, fractions were obtained from sequential extraction of the crude extract using solvents of increasing polarity. Dose responses corresponding to cell survival following 72-hour exposure to the extracts were determined using a leukaemia cancer cell line (MT-4). Cell viability was assessed using the MTT[3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide] assay reading absorbances at 570 nm. Comparisons were made with controls and cell survival, in each sample well, was determined based on the ratio of the absorbance of the sample to the control. RESULTS: Crude extracts of S verticillata, F pumila and F strobilifera displayed cytotoxicity and the IC50 values were 89 microg/ml, 131 microg/ml and 81 microg/ml, respectively. The petroleum ether and chloroform fractions of the crude extracts of S verticillata and F strobilifera showed potent cytotoxic activity but the highest cytotoxic activity was found in the chloroform and butanol fractions of F pumila with IC50 values of 23 microg/ml and 26 microg/ml, respectively. CONCLUSION: The crude extracts of S verticillata, F pumila and F strobilifera were shown to be cytotoxic to the leukaemia cell line, MT-4 and IC50 values were determined. Fractionation of the crude extracts by solvent-solvent extraction enabled determination of the active fractions and their IC50 values. We propose that cytotoxic activity may be due to antioxidant compounds previously isolated from these plants.

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Two new bis(monoterpenoid) indole alkaloid glucosides, bahienoside A (1) and bahienoside B (2), together with five known compounds, 5alpha-carboxystrictosidine, angustine, strictosamide, and (E)- and (Z)-vallesiachotamine, were isolated from the aerial parts of Psychotria bahiensis collected in Trinidad, West Indies. The structures of the compounds were elucidated using 1D and 2D NMR spectral methods, viz., (1)H, (13)C, (13)C DEPT, (1)H-(1)H COSY, HSQC, HMQC, HMBC, and TOCSY aided by IR, UV, and circular dichroism measurements.

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A number of crude extracts from folk medicinal plants were screened for cytotoxicity against the human T-cell leukemia cell line. Fixed aliquots from a quantified cell suspension were incubated for three days in the presence of a control and several different concentrations of the given plant extract

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Bioassay-guided fractionation of the methanol extracts of the aerial parts of Psychotria uliginosa Sw yielded four known bioactive compounds: benz[g]isoquinoline-5,10-dione and 1-hydroxy-4,7-megastigmadien-3-one and blumenol A, which are chemically related to S-(+)-dehydrovomifoliol a known inhibitor of the germination of lettuce seeds. Evaluation of the basic components obtained from the methanol extract of the aerial parts of Psychotria bahiensis DC. yielded five bioactive indole monoterpenoid alkaloids which are known to display various levels of antiplasmodial and antitumor activity: 5 alpha-carboxystrictosidine, angustine, strictosamide and (E) and (Z)-vallesiachotamine; and the novel epimers bahienoside A and B which are currently being investigated for biological activity. The structures were determined by means of 1D and 2D NMR techniques

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Accurate evaluation of patients with suspected or known cutaneous lymphoma requires the integration of many sources and types of information, including clinical evaluation, microscopic analysis of tissue, immunophenotyping, gene rearrangement studies, clinical staging, and longitudinal observation. Diagnoses should be based on knowledge of specific lymphoma types as described in modern classification systems. Management of patients with cutaneous lymphoma requires collaboration among dermatologists, dermatopathologists, hematopathologists, and medical, surgical and radiation oncologists. (J Am Acad Dermatol 2002;46:325-57.) LEARNING OBJECTIVE: At the conclusion of this learning activity, participants should better understand how to evaluate and manage patients for suspected or established lymphoma of the skin. Components include the clinical history and physical examination, optimal biopsy and tissue handling, interpretation of pathology and adjunctive test results, clinicopathologic correlation, and therapy. Participants should also understand the basis for establishing a specific diagnosis of cutaneous lymphoma based on current classification and staging.

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Se analizan los resultados de la reconstrucción plástica de la válvula mitral en forma aislada (Grupo 1; n: 68) o combinada con otros procedimientos quirúrgicos (Grupo 2; n: 67) en 135 pacientes. En el 97 por ciento de los casos se efectuó anuloplastia sin anillos protésicos y en la mayoría con pericardio autólogo. La mortalidad hospitalaria fue del 4 por ciento en el Grupo 1 y del 12 por ciento en el Grupo 2. La probabilidad de permanecer libre de reoperación a 1,3 y 5 años es de 96 por ciento, 94 por ciento y 86 por ciento respectivamente; la probabilidad de sobrevida a 1, 3 y 5 años es de 91 por ciento, 89 por ciento y 89 por ciento respectivamente en el Grupo 1 y 86 por ciento, 70 por ciento y 62 por ciento respectivamente en el Grupo 2. La reparación mitral es posible sin la utilización de anillos protésicos, con buenos resultados inmediatos y a mediano plazo (AU)

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Se analizan los resultados de la reconstrucción plástica de la válvula mitral en forma aislada (Grupo 1; n: 68) o combinada con otros procedimientos quirúrgicos (Grupo 2; n: 67) en 135 pacientes. En el 97 por ciento de los casos se efectuó anuloplastia sin anillos protésicos y en la mayoría con pericardio autólogo. La mortalidad hospitalaria fue del 4 por ciento en el Grupo 1 y del 12 por ciento en el Grupo 2. La probabilidad de permanecer libre de reoperación a 1,3 y 5 años es de 96 por ciento, 94 por ciento y 86 por ciento respectivamente; la probabilidad de sobrevida a 1, 3 y 5 años es de 91 por ciento, 89 por ciento y 89 por ciento respectivamente en el Grupo 1 y 86 por ciento, 70 por ciento y 62 por ciento respectivamente en el Grupo 2. La reparación mitral es posible sin la utilización de anillos protésicos, con buenos resultados inmediatos y a mediano plazo

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A number of crude extracts from folk medicinal plants were screened for cytotoxicity against the human T-cell leukemia cell line. Fixed aliquots from a quantified cell suspension were incubated for three days in the presence of a control and several different concentrations of the given plant extract

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Bioassay-guided fractionation of the methanol extracts of the aerial parts of Psychotria uliginosa Sw yielded four known bioactive compounds: benz[g]isoquinoline-5,10-dione and 1-hydroxy-4,7-megastigmadien-3-one and blumenol A, which are chemically related to S-(+)-dehydrovomifoliol a known inhibitor of the germination of lettuce seeds. Evaluation of the basic components obtained from the methanol extract of the aerial parts of Psychotria bahiensis DC. yielded five bioactive indole monoterpenoid alkaloids which are known to display various levels of antiplasmodial and antitumor activity: 5 alpha-carboxystrictosidine, angustine, strictosamide and (E) and (Z)-vallesiachotamine; and the novel epimers bahienoside A and B which are currently being investigated for biological activity. The structures were determined by means of 1D and 2D NMR techniques (AU)

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