Permanent control of HIV-1 pathogenesis in exceptional elite controllers: a model of spontaneous cure

Elite controllers (EC) represent a small subset of HIV-1-infected people that spontaneously control viral replication. However, natural virological suppression and absence of immune dysfunction are not always long-term sustained. We define exceptional EC (EEC) as HIV-1 subjects who maintain the EC characteristics without disease progression for more than 25 years. We analyzed three EEC, diagnosed between 1988 and 1992, who never showed signs of clinical disease progression in absence of any antiretroviral treatment. A comprehensive clinical, virological, and immunological study was performed. The individuals simultaneously exhibited ≥3 described host protective alleles, low levels of total HIV-1 DNA (0.50). Inflammation levels of EEC were similar to HIV-1 negative donors. Remarkably, they showed an exceptional lack of viral evolution and 8-fold lower genetic diversity (<0.01 s/n) in env gene than other EC. We postulate that these EEC represent cases of spontaneous functional HIV-1 cure. A non-functional and non-genetically evolving viral reservoir along with an HIV-1-specific immune response seems to be key for the spontaneous functional cure.Work in Centro Nacional de Microbiologia (ISCIII) was supported by grants SAF (2016–77894-R) from Ministerio de Economia y Competitividad (MINECO) (Spain) and Fondo de Investigación Sanitaria (FIS)-Instituto de Salud CarlosIII, grant FIS (PI 13/02269, ISCIII) and in part by the RIS-RETIC grants RD12/0017/0028 and RD16CIII/0002/0005 funded by the ISCIII-FEDER. MP has a contract of RIS-RETIC RD16CIII/0002/0005. This work was supported by grants from the MINECO, FIS-Instituto de Salud CarlosIII, Fondos Europeos para el Desarrollo Regional, FEDER, grant numbers PI16/00684, PI19/01127, CPII014/00025 to ER-M. and FI14/00431 to LT-D.; the Gilead Fellowship Program (grant numbers GLD17/00299); the Red de Investigación en Sida (grant number RD16/0025/0020). ER-M. is supported by Consejería de Salud y Bienestar Social of Junta de Andalucía through the Nicolás Monardes Program (C-0032/17). Research in VS-M group was supported by Fondo de Investigación Sanitaria (FIS)-Instituto de Salud CarlosIII, grant FIS (PI 17CIII/00049). Grifols partially supported work in the AIDS Research Institute IrsiCaixa. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.S

Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research

Ileocolic intussusception due to giant ileal lipoma: Review of literature and report of a case

AbstractINTRODUCTIONIntussusception in adults accounts for less than 5% of all intussusceptions. It occurs when a segment of intestine invaginates into itself.PRESENTATION OF A CASEWe report a case of ileocolic intussusception in an adult caused by a giant ileal lipoma.DISCUSSIONIntussusceptions can be classified as ileocolic, ileocecal, colo-colic and ileo-ileal. Most are due to neoplasms (60% malign and 24–40% benign). In the colon, the possibility of malignancy is higher than in small intestine.Lipomas are the most common benign mesenchymal intestinal tumors, accounting for less than 5% of all gastrointestinal tumors. They are more frequent in colon than small intestine. Small lipomas (less than 2cm) are usually asymptomatic. Larger lesions may produce symptoms such as abdominal pain, obstruction or intussusception. Lipomas can be diagnosed with endoscopy, capsule endoscopy, barium enemas, CT and US.CONCLUSIONIntussusceptions in adults is a rare condition, most of them are caused by a malign neoplasms followed by benign neoplasms. US and CT are useful for diagnosis. Surgery is mandatory

Plan de negocios para una agencia de turismo receptivo boutique orientado al mercado norteamericano

El Perú es un país milenario y conocido por su autenticidad, cultura ancestral, biodiversidad y en estos últimos años por su Gastronomía, reconocida y premiada a nivel mundial. Sus atractivos turísticos y la importancia de contar con una de las siete maravillas del mundo, la ciudadela de “Machu Picchu”, es una razón más y la más importante para visitar el Perú; ello lo sitúa a nivel mundial en el puesto diez del ranking de mejores destinos turísticos con 3.2 millones de visitas al año y con un crecimiento sostenido en los últimos tres. Las agencias de turismo actualmente se ven enfocadas en productos masivos, sin embargo la tendencia mundial exige personalización con productos a medida que permitan y beneficien experiencias memorables con recuerdos perecederos principalmente en productos de lujo. El objetivo de este plan de negocios es aportar al desarrollo de la industria turística, buscando articular una oferta con servicios temáticos que resalten los atributos por los cuales el Perú cada día logra ser más reconocido a nivel mundial. Por ello Illari Luxury Travel, como agencia de viajes personalizará la oferta a los vacacionistas, con servicios asociados a la experiencia de tres reconocidos gestores locales con amplia trayectoria y conocimiento en cada una de las propuestas. Como negocio busca ampliar los límites de la oferta apelando a los sentimientos y emociones de los vacacionistas a través de su participación activa y permanente en cada una de las actividades que elijan. La garantía del servicio se soporta en tres grandes especialistas: Perú Ancestral con Alfredo Mormontoy, reconocido arqueólogo cuzqueño, personaje líder en la restauración de la ciudadela de Machu Picchu. Perú Gastronómico con Mauricio Fernandini, periodista y conductor del programa 20 Lucas, muy reconocido por su recorrido a los diferentes huariques. Perú Biodiverso con Manolo Del Castillo, periodista apasionado por la aventura y la diversidad con amplio conocimiento de las zonas más agrestes del país. Se considera también como estrategia de marketing la invitación del líder de opinión internacional, Anthony Bourdain (conductor Travel Chanel) con un viaje de reconocimiento acompañado por los especialistas de Illari Luxury Travel para dar a conocer los servicios personalizados. Illari Luxury Travel tiene como objetivo para el primer año de operación conseguir una participación de 0.25% del total de mercado, lo que equivale a 232 turistas considerados el mejor prospecto provenientes de Estados Unidos y Canadá que perciben más de $80.000 al año, para el año cinco proyecta atender a 424 turistas. Cumplir con el objetivo de participación lleva al negocio a generar una utilidad neta positiva de 3% a partir del segundo año con proyección al quinto año de 29%. La inversión requerida para el proyecto es de S/.338, 000 compuesta de un aporte de capital de S/. 130.000 y un financiamiento bancario de S/. 238.000 con una tasa de interés anual efectiva de 25% a 6 años. Como resultado un VAN Financiero de S/. 290.388, una TIR de 55.80% y un Costo promedio de capital de 23.68%. Este plan de negocios además va orientado a aportar con el desarrollo turístico del Perú y a promocionarlo de una manera diferente gracias a sus propuestas flexibles, personalizadas y exclusivas para aquel mercado exigente y conocedor del mundo.Tesi

Unusual Case of Gallbladder Adenocarcinoma Metastasis to the Abdominal Wall 11 Years Later: Synchronous Presentation with Two Malignant Colon Tumors, Coincidence or Not?

Introduction. Abdominal wall masses are a common finding in clinical practice. A high percentage of these masses are malignant. We present the case of a patient operated for a gallbladder adenocarcinoma, who consulted eleven years later for a malignant mass of the abdominal wall in synchrony with two adenocarcinomas of the left colon and sigmoid. Case Report. A 75-year-old male underwent a laparoscopic cholecystectomy with an incidental diagnosis of adenocarcinoma in situ (TisN0M0 according to AJCC 8th edition). The operative report mentioned that the removal of the gallbladder was difficult due to the inflammatory process, and the gallbladder was accidentally opened during the operation. It was not clear from the operative report whether an extraction bag was utilized to remove the specimen, but the histopathological study confirmed an open gallbladder. He presented 11 years later with an asymptomatic heterogeneous complex cystic mass involving the anterior rectus abdominis muscle. Colonoscopy showed synchronous tumors in the descending and sigmoid colon with pathology confirming adenocarcinoma. The patient underwent an elective laparotomy with resection of the anterior abdominal wall mass, left hemicolectomy, and sigmoidectomy. The histopathological results of the abdominal mass (CK7, CK20, EMA, CEA positive) were described as metastasis of adenocarcinoma of biliary origin. Discussion. Port site recurrences are rare complications following laparoscopic surgery when malignancy is unsuspected. Possible factors related to local implantation include direct seeding of spilled bile or tumor cells into the wound or shedding of tumor cells due to pneumoperitoneum-induced loss of the peritoneal barrier at the trocar site. In the absence of distant metastasis, treatment should include wide port site excision with malignancy-free surgical margins. Conclusion. Abdominal wall metastasis from gallbladder carcinoma is rare, and its synchronous presentation with a malignant neoplasm of the colon is exceptional. This is the first report of a patient with abdominal wall metastasis from a gallbladder adenocarcinoma operated eleven years ago that debuted synchronously with two adenocarcinomas of the left colon and sigma

Prognostic Factors of Survival in Patients with Peritoneal Metastasis from Colorectal Cancer

Objectives: The aim of this study was to analyze the prognostic factors of survival in patients with peritoneal metastasis (PM) from colorectal cancer (CRC). The type of relationship between survival and the PM time of detection was used to determine whether it was synchronous with the primary tumor or metachronous. Patients and Methods: Retrospective observational study. It included patients treated for colorectal adenocarcinoma diagnosed between January 2005 and December 2019 who presented PM at the time of diagnosis or during follow-up. Variables, such as sex, age, differentiation grade, positive adenopathy (pN+), tumor size (pT), tumor location, mucinous component, peritoneal carcinomatosis index (PCI), and KRAS mutational status, were analyzed. Results: During the study period, 1882 patients were surgically treated for CRC in our hospital. Of these, 240 patients (12.8%) were included in the study after evidence of PM. The mean age was 67 &plusmn; 12 years (range: 32&ndash;92 years), and 114 patients were female (47.5%). The mean follow-up was 20 &plusmn; 13 months (median 12 months). The Kaplan&ndash;Meier survival at 36 months was higher in patients with metachronous PM (24% vs. 8%; p = 0.002), WT-KRAS tumors (31% vs. 15%; p &lt; 0.001), N0 stage (30% vs. 19%; p &lt; 0.001), T3 stage tumors (18% vs. 19% in T4A and 3% in T4B; p &gt; 0.001), and tumors with classic adenocarcinoma histology (18% vs. 8%; p = 0.011). Patients with a PCI of 1&ndash;10 showed a likelihood of survival at 36 months of 56%, which was longer than that found in patients with a PCI of 11&ndash;20 (8%) or a PCI of &gt;20 (0%) (p &lt; 0.001). In the multiple regression analysis, the factors with an independent prognostic value were: poor grade of differentiation (HR 1.995; 95% CI: 1.294&ndash;3.077), KRAS mutation (HR 1.751; 95% CI: 1.188&ndash;2.581), PCI 11&ndash;20 (HR: 9.935; 95% CI: 5.204&ndash;18.966) and PCI &gt; 20 (HR: 4.011; 95% CI: 2.291&ndash;7.023). Conclusions: PCI should continue as the as the most useful prognostic indicator in order to assess prognostic estimations as well as therapeutic and surgical decisions, but tumor grade and KRAS mutational status may help in the treatment decision process by providing complementary information. The time of PM detection did not achieve statistical significance in the multiple regression analysis