Correction to: Gout In Extremis: Massive Soft Tissue Tophaceous Deposits.

This paper was originally published with open access, but has since been granted retrospective open access cancellation.

Mitomycin C and its analog trigger cytotoxicity in MCF-7 and K562 cancer cells through the regulation of RAS and MAPK/ERK pathways.

Mitomycin C (MC) is an anti-cancer drug which functions by forming interstrand crosslinks (ICLs) between opposing DNA strands. MC analog, 10-decarbamoyl mitomycin C (DMC), unlike MC, has stronger cytotoxic effects on cancer cells with TP53 mutation. We previously demonstrated that MC/DMC could activate p21WAF1/CIP1 in MCF-7 (TP53-proficient) and K562 (TP53 deficient) cells in a TP53-independent mode. We also found that MC/DMC regulate AKT activation in a TP53-dependent manner and that AKT deactivation is not associated with the activation of p21WAF1/CIP1 in response to MC/DMC treatment. RAS proteins are known players in the upstream mediated signaling of p21WAF1/CIP1 activation that leads to control of cell proliferation and cell death. Thus, this prompted us to investigate the effect of both drugs on the expression of RAS proteins and regulation of the MAPK/ERK signaling pathways in MCF-7 and K562 cancer cells. To accomplish this goal, we performed comparative label free proteomics profiling coupled to bioinformatics/complementary phosphoprotein arrays and Western blot validations of key signaling molecules. The MAPK/ERK pathway exhibited an overall downregulation upon MC/DMC treatment in MCF-7 cells but only DMC exhibited a mild downregulation of that same pathway in TP53 mutant K562 cells. Furthermore, treatment of MCF-7 and K562 cell lines with oligonucleotides containing the interstrand crosslinks (ICLs) formed by MC or DMC shows that both ICLs had a stronger effect on the downregulation of RAS protein expression in mutant TP53 K562 cells. We discuss the implication of this regulation of the MAPK/ERK pathway in relation to cellular TP53 status.

Single-Center Experience With the Seraph-100® Microbind® Affinity Blood Filter in Patients With SARS-CoV-2 Infection and Septic Shock at a Military Treatment Facility.

INTRODUCTION: Coronavirus disease 2019 (COVID-19) infection is characterized by a dysregulated inflammatory response, which may result in severe hemodynamic instability and septic shock. The Seraph-100® Microbind® Affinity Blood Filter is a commercially available extracorporeal pathogen absorbent device with the ability to bind pathogens and cytokines present within the blood. Our study aimed to evaluate the efficacy of the Seraph-100® for patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and septic shock. MATERIALS AND METHODS: A retrospective review was performed to evaluate the use of the Seraph-100® blood filter at a Single Center tertiary-care facility at Brooke Army Medical Center from 2020 to 2021. Nine patients (11 treatments) were completed with the Seraph-100® blood filter in patients with SARS-CoV-2 infection and septic shock. The Seraph-100® blood filter was used in combination with continuous renal replacement therapy and slow low-efficiency dialysis or directly in parallel with the extracorporeal membrane oxygenation circuit. RESULTS: Within this cohort, there was a statistically significant improvement in the following clinical parameters comparing values to before and after treatment with the Seraph-100® blood filter: Mean arterial pressure (mmHg) (64.2 ± 2.36 vs. 76.2 ± 2.68; P < .001), heart rate (beats per minute) (128 ± 6.6 vs. 100.3 ± 6.07; P < .001), administered fraction of oxygen (%) (74.4 ± 10.58 vs. 60.3 ± 10.35; P < .001), serum lactate (mmol/L) (6.14 ± 1.25 vs. 2.8 ± 1.14; P = .0095), and pH (7.29 ± 0.03 vs. 7.39 ± 0.04; P = .0203). There were statistically significant improvements in vasopressor requirements: norepinephrine (mcg/min) (36.3 ± 4.74 vs. 8.3 ± 3.92; P < .001), vasopressin (units/min) (0.04 ± 0.004 vs. 0.02 ± 0.003; P < .001), dobutamine (mcg/kg/min) (2.3 ± 1.00 vs. 0.2 ± 0.75; P = .006) and angiotensin II (ng/kg/min) (34.5 ± 6.4 vs. 3.3 ± 5.26; P < .001). CONCLUSIONS: The use of the Seraph-100® blood filter was associated with statistically and clinically significant improvements in hemodynamic parameters and decreased vasopressor requirements in patients with septic shock and SARS-CoV-2 infection.

Electrocardiographic differentiation of early repolarization from subtle anterior ST-segment elevation myocardial infarction.

STUDY OBJECTIVE: Anterior ST-segment elevation myocardial infarction (STEMI) can be difficult to differentiate from early repolarization on the ECG. We hypothesize that, in addition to ST-segment elevation, T-wave amplitude to R-wave amplitude ratio (T-wave amplitude(avg)/R-wave amplitude(avg)), and R-wave amplitude in leads V2 to V4, computerized corrected QT interval (QTc) and upward concavity would help to differentiate the 2. We seek to determine which ECG measurements best distinguish STEMI versus early repolarization. METHODS: This was a retrospective study of patients with anterior STEMI (2003 to 2009) and early repolarization (2003 to 2005) at 2 urban hospitals, one of which (Minneapolis Heart Institute) receives 500 STEMI patients per year. We compared the ECGs of nonobvious ("subtle") anterior STEMI with emergency department noncardiac chest pain patients with early repolarization. ST-segment elevation at the J point and 60 ms after the J point, T-wave amplitude, R-wave amplitude, QTc, upward concavity, J-wave notching, and T waves in V1 and V6 were measured. Multivariate logistic regression modeling was used to identify ECG measurements independently predictive of STEMI versus early repolarization in a derivation group and was subsequently validated in a separate group. RESULTS: Of 355 anterior STEMIs identified, 143 were nonobvious, or subtle, compared with 171 early repolarization ECGs. ST-segment elevation was greater, R-wave amplitude lower, and T-wave amplitude(avg)/R-wave amplitude(avg) higher in leads V2 to V4 with STEMI versus early repolarization. Computerized QTc was also significantly longer with STEMI versus early repolarization. T-wave amplitude did not differ significantly between the groups, such that the T-wave amplitude(avg)/R-wave amplitude(avg) difference was entirely due to the difference in R-wave amplitude. An ECG criterion based on 3 measurements (R-wave amplitude in lead V4, ST-segment elevation 60 ms after J-point in lead V3, and QTc) was derived and validated for differentiating STEMI versus early repolarization, such that if the value of the equation ([1.196 x ST-segment elevation 60 ms after the J point in lead V3 in mm]+[0.059 x QTc in ms]-[0.326 x R-wave amplitude in lead V4 in mm]) is greater than 23.4 predicted STEMI and if less than or equal to 23.4, it predicted early repolarization in both groups, with overall sensitivity, specificity, and accuracy of 86% (95% confidence interval [CI] 79, 91), 91% (95% CI 85, 95), and 88% (95% CI 84, 92), respectively, with positive likelihood ratio 9.2 (95% CI 8.5 to 10) and negative likelihood ratio 0.1 (95% CI 0.08 to 0.3). Upward concavity, upright T wave in V1 or T wave, in V1 greater than T wave in V6, and J-wave notching did not provide important information. CONCLUSION: R-wave amplitude is lower, ST-segment elevation greater, and QTc longer for subtle anterior STEMI versus early repolarization. In combination with other clinical data, this derived and validated ECG equation could be an important adjunct in the diagnosis of anterior STEMI.

Outcomes of Fungemia in Patients Receiving Extracorporeal Membrane Oxygenation.

There are limited data on the treatment of fungal infections complicating extracorporeal membrane oxygenation (ECMO). In 14 patients who developed fungal bloodstream infections on ECMO, 8 (57%) survived to discharge. Of the 5 patients completing treatment prior to decannulation, 2 (40%) developed recurrent fungal infections.

Laparoendoscopic single-site Heller myotomy with anterior fundoplication for achalasia.

BACKGROUND: Laparoendoscopic single-site (LESS) surgery is beginning to include advanced laparoscopic operations such as Heller myotomy with anterior fundoplication. However, the efficacy of LESS Heller myotomy has not been established. This study aimed to evaluate the authors' initial experience with LESS Heller myotomy for achalasia. METHODS: Transumbilical LESS Heller myotomy with concomitant anterior fundoplication for achalasia was undertaken for 66 patients after October 2007. Outcomes including operative time, complications, and length of hospital stay were recorded and compared with those for an earlier contiguous group of 66 consecutive patients undergoing conventional multi-incision laparoscopic Heller myotomy with anterior fundoplication. Symptoms before and after myotomy were scored by the patients using a Likert scale ranging from 0 (never/not severe) to 10 (always/very severe). Data were analyzed using the Mann-Whitney U test, the Wilcoxon matched-pairs test, and Fisher's exact test where appropriate. RESULTS: Patients undergoing LESS Heller myotomy were similar to those undergoing conventional laparoscopic Heller myotomy in gender, age, body mass index (BMI), blood loss, and length of hospital stay. However, the patients undergoing LESS Heller myotomies had operations of significantly longer duration (median, 117 vs. 93 min with the conventional laparoscopic approach) (p<0.003). For 11 patients (16%) undergoing LESS Heller myotomy, additional ports/incisions were required. No patients were converted to "open" operations, and no patients had procedure-specific complications. Symptom reduction was dramatic and satisfying after both LESS and conventional laparoscopic myotomy with fundoplication. The symptom reduction was similar with the two procedures. The LESS approach left no apparent umbilical scar. CONCLUSION: Heller myotomy with anterior fundoplication effectively treats achalasia. The findings showed LESS Heller myotomy with anterior fundoplication to be feasible, safe, and efficacious. Although the LESS approach increases operative time, it does not increase procedure-related morbidity or hospital length of stay and avoids apparent umbilical scarring. Laparoendoscopic single-site surgery represents a paradigm shift to more minimally invasive surgery and is applicable to advanced laparoscopic operations such as Heller myotomy and anterior fundoplication.

A single institution's experience with more than 500 laparoscopic Heller myotomies for achalasia.

BACKGROUND: Long-term symptom relief and patient satisfaction after Heller myotomy are being reported. Herein, we report the largest experience of laparoscopic Heller myotomy for the treatment of achalasia. STUDY DESIGN: Since 1992, 505 patients have been prospectively followed after laparoscopic Heller myotomy. Until 2004, concomitant fundoplication was undertaken for a patulous hiatus, a large hiatal hernia, or to buttress the repair of an esophagotomy, then concomitant fundoplication became routinely applied. More recently, laparo-endoscopic single site (LESS) Heller myotomy has been performed when possible to improve cosmesis. Before and after myotomy, patients scored their symptoms. RESULTS: Before myotomy, 60% of patients underwent endoscopic therapy; of these patients, 27% had Botox (Allergan) therapy alone, 52% underwent dilation therapy alone, and 21% had both. Esophagotomy occurred in 7% of patients. Concomitant diverticulectomy was undertaken in 7%, fundoplication was performed in 59%, and LESS Heller myotomy was done in 12%. Median length of stay was 1 day. With mean follow-up at 31 months, the severity of all symptoms improved significantly. After myotomy, 95% experienced symptoms less than once per week, 86% believed their outcome is satisfying or better, and 92% would undergo myotomy again, if necessary. Symptoms after myotomy are similar with or without fundoplication and regardless of the laparoscopic approach used. CONCLUSIONS: Laparoscopic Heller myotomy safely and durably relieves symptoms of dysphagia. Confinement is short and satisfaction is very high. Relief of esophageal obstruction is paramount; the approach used or the application of a fundoplication has a lesser impact. Laparoscopic Heller myotomy, preferably with anterior fundoplication using a single site laparoscopic approach, is strongly encouraged for patients with symptomatic achalasia and is efficacious even after failures of dilation and/or Botox therapy.

Una taxonomía para el análisis de descripciones pre y post contacto con arreglos contingenciales / A taxonomy of the analysis of pre and post contingency contact descriptions / Uma taxonomia para a análise de descrições pré e pós-contato com arranjos contingenciais

Existen en la literatura suficientes datos para tratar de establecer diferencias funcionales entre instrucciones y reglas. En un intento para distinguirlos, el presente trabajo se basa en la idea de que, aun cuando instrucciones y reglas son descripciones de contingencias particulares, difieren en el momento, la fuente y su función en la adquisición y mantenimiento de conducta. Se asume que cualquier situación, tanto experimental como no experimental, está integrada por tres componentes: a) la situación de estímulo (SE), 2) la respuesta (R) del sujeto y, 3) las consecuencias de dicha respuesta (C). La descripción hecha acerca de cada uno de estos componentes puede poseer cuatro cualidades: a) presencia, b) relevancia, c) especificidad y, d) pertinencia. Dichas cualidades son inclusivas y los valores registrados para cada una de ellas son su valores opuestos (i.e. presencia-ausencia, relevante-irrelevante, genérico-específico, pertinente-no pertinente). Podemos identificar seis categorías para clasificar cualquier descripción, cuatro de ellas resultados de la combinación de los valores de las cualidades especificidad y pertinencia, una basada en la mención de elementos irrelevantes y, una sexta, basada en la falta de mención de cualquiera de los elementos. Esta propuesta puede constituir una herramienta útil para el estudio y análisis de descripciones contingenciales.

There is enough data in the literature to support an argument showing functional differences between instructions and rules. In an attempt to distinguish these elements, this paper presents the argument that even though instructions and rules are descriptions of particular contingencies, they differ in: a) the moment in which the subject describes the contingency, b) the description’s source, and c) their function in behaviour acquisition and maintenance. It can be assumed that any situation, both experimental and non-experimental, is made up of three components: 1) stimulus situation (SS), 2) subject’s response (R), and 3) response’s consequences (C). The description made about each component often possesses four qualities: a) presence, b) relevance, c) specificity, and d) pertinence. These qualities are inclusive and the registered values are the opposite sides of each one (i.e. presence-absence, relevant-irrelevant, generic-specific, pertinent-non pertinent). Should rules and instructions considered to be descriptions of a contingencial array, it would be necessary to have a taxonomy that allows analysis and qualification under similar assessment criteria. Any description can be classified into six identifiable categories; four of them, result from a combination of quality values (i.e. specificity and pertinence), the fifth is based on the mention of irrelevant elements, and the sixth is based on the non-mention of any of the elements: 1) Specific and pertinent (SP), 2) Specific and Non-Pertinent (SNP), 3) Generic and Pertinent (GP), 4 Generic and Non-pertinent (GNP), 5) Irrelevant (I), and 6) Absent (A). This proposal can constitute a useful tool for the study and analysis of contingencial descriptions (i.e. instructions and rules).

Na literatura há suficientes dados para tratar de estabelecer diferenças funcionais entre instruções e regras. No intuito por distingui-los, este trabalho postula que, mesmo se e instruções e regras são descrições de contingências particulares, diferem no momento, na fonte e a sua função na aquisição e manutenção da conduta. Assume-se que qualquer situação, experimental ou não experimental, é integrada por três componentes: 1) a situação de estímulo (SE), 2) a resposta (R) do sujeito e 3) as conseqüências dessa resposta (C). A descrição de cada um destes componentes pode possuir quatro qualidades: presença, relevância, especificidade e pertinência. Estas qualidades são inclusivas, e os valores registrados para cada uma delas são os seus valores contrários (por exemplo, presença-ausência, relevância-irrelevância, genérico-específico, pertinente, não-pertinente). Se podem identificar seis categorias para classificar qualquer descrição: quatro são o resultado de combinar os valores das qualidades especificidade e pertinências a combinação, uma baseada na menção de elementos irrelevantes e outra fundada na falta de menção de qualquer um dos elementos. Esta proposta pode ser um instrumento útil para estudar e analisar descrições contingenciais.