Casein kinase 2 phosphorylates and induces the SALL2 tumor suppressor degradation in colon cancer cells.

Spalt-like proteins are Zinc finger transcription factors from Caenorhabditis elegans to vertebrates, with critical roles in development. In vertebrates, four paralogues have been identified (SALL1-4), and SALL2 is the family's most dissimilar member. SALL2 is required during brain and eye development. It is downregulated in cancer and acts as a tumor suppressor, promoting cell cycle arrest and cell death. Despite its critical functions, information about SALL2 regulation is scarce. Public data indicate that SALL2 is ubiquitinated and phosphorylated in several residues along the protein, but the mechanisms, biological consequences, and enzymes responsible for these modifications remain unknown. Bioinformatic analyses identified several putative phosphorylation sites for Casein Kinase II (CK2) located within a highly conserved C-terminal PEST degradation motif of SALL2. CK2 is a serine/threonine kinase that promotes cell proliferation and survival and is often hyperactivated in cancer. We demonstrated that CK2 phosphorylates SALL2 residues S763, T778, S802, and S806 and promotes SALL2 degradation by the proteasome. Accordingly, pharmacological inhibition of CK2 with Silmitasertib (CX-4945) restored endogenous SALL2 protein levels in SALL2-deficient breast MDA-MB-231, lung H1299, and colon SW480 cancer cells. Silmitasertib induced a methuosis-like phenotype and cell death in SW480 cells. However, the phenotype was significantly attenuated in CRISPr/Cas9-mediated SALL2 knockout SW480 cells. Similarly, Sall2-deficient tumor organoids were more resistant to Silmitasertib-induced cell death, confirming that SALL2 sensitizes cancer cells to CK2 inhibition. We identified a novel CK2-dependent mechanism for SALL2 regulation and provided new insights into the interplay between these two proteins and their role in cell survival and proliferation.

[Features of patients admitted with COVID-19 to a Chilean regional hospital during the first stages of the pandemic]. / COVID-19 en adultos en el Hospital de Puerto Montt en la primera etapa de la pandemia.

BACKGROUND: The COVID-19 pandemic posed a great strain in health services. AIM: To describe the epidemiological and clinical features of patients with SARS-CoV-2 admitted to a regional hospital in southern Chile between April and August 2020. MATERIAL AND METHODS: Clinical records of all hospitalized patients with RT-PCR (+) for SARS-CoV-2 were retrospectively analyzed. RESULTS: During the study period 226 patients aged 55 ± 18 years (55% men) were admitted. The main comorbidities were high blood pressure in 45%, diabetes in 31% and obesity in 21%. The main symptoms were dyspnea in 70%, cough in 69%, fever in 62% and myalgia in 47%. Pneumonia was the main cause of admission in 66%. Images on admission were compatible with pneumonia in 81%, and with a typical COVID-19 pattern in 84%. In 76% there was five-lobe involvement. Eighty-seven cases (39%) were admitted to critical care, with an APACHE score of 10.9 ± 7.1. Invasive mechanical ventilation was used in 16%, 30% required prone position and 13%, a high-flow nasal cannula. The mean stay in critical care was 13.3 days. The mean duration of invasive mechanical ventilation was 14.1 days. Antimicrobials were used in 55% and dexamethasone in 36%. Twenty-two (9.7%) patients aged 71.7 ± 14 died. A Charlson comorbidity index > 3, heart failure and connection to invasive mechanical ventilation were independent risk factors for death. An age > 65 years alone and other comorbidities were not risk factors. CONCLUSIONS: Viral pneumonia is the main cause of hospitalization for COVID-19, usually extensive and bilateral. The greater severity and poor prognosis of these patients are mainly related to comorbidities.

[Clinical and epidemiological differences and similarities of viral pneumonias in two pandemics]. / Diferencias y similitudes clínicas y epidemiológicas de la neumonía viral en dos pandemias.

BACKGROUND: In a decade, we faced two pandemic viruses, influenza A H1N1pdm09 and SARS CoV-2, whose most serious manifestation is pneumonia. AIM: To compare the clinical, epidemiological and management aspects of pneumonias caused by each pandemic virus in adults requiring hospitalization. MATERIAL AND METHODS: Comparative, observational study carried out at a regional Chilean hospital, including 75 patients with influenza A H1N1pdm09 prospectively studied in 2009 and 142 patients with SARS-CoV-2 studied in 2020. RESULTS: Patients with SARS-CoV-2 pneumonia were older (56 and 39.7 years respectively, p < 0.01) and had significantly more comorbidities. Cough, fever and myalgias were more frequent in influenza. Dyspnea was more frequent in COVID-19. Patients with COVID-19 had more extensive lung involvement and a longer hospitalization (13.6 and 8.6 days respectively, p = 0.01). There was no difference on ICU admission requirements and mortality attributable to pneumonia. Patients with influenza had greater APACHE scores and a higher frequency of a PaO2/FiO2 ratio ≤ 200. During COVID-19pandemic chest sean replaced x-ray examination. Also high-flow nasal cannulas and awake prone position ventilation were added as treatments. CONCLUSIONS: COVID-19 patients were older, had fewer classic flu symptoms but more dyspnea and longer hospitalization periods than patients with influenza.

COVID-19 en adultos en el Hospital de Puerto Montt en la primera etapa de la pandemia / Features of patients admitted with COVID-19 to a Chilean regional hospital during the first stages of the pandemic

BACKGROUND: The COVID-19 pandemic posed a great strain in health services. AIM: To describe the epidemiological and clinical features of patients with SARS-CoV-2 admitted to a regional hospital in southern Chile between April and August 2020. MATERIAL AND METHODS: Clinical records of all hospitalized patients with RT-PCR (+) for SARS-CoV-2 were retrospectively analyzed. RESULTS: During the study period 226 patients aged 55 ± 18 years (55% men) were admitted. The main comorbidities were high blood pressure in 45%, diabetes in 31% and obesity in 21%. The main symptoms were dyspnea in 70%, cough in 69%, fever in 62% and myalgia in 47%. Pneumonia was the main cause of admission in 66%. Images on admission were compatible with pneumonia in 81%, and with a typical COVID-19 pattern in 84%. In 76% there was five-lobe involvement. Eighty-seven cases (39%) were admitted to critical care, with an APACHE score of 10.9 ± 7.1. Invasive mechanical ventilation was used in 16%, 30% required prone position and 13%, a high-flow nasal cannula. The mean stay in critical care was 13.3 days. The mean duration of invasive mechanical ventilation was 14.1 days. Antimicrobials were used in 55% and dexamethasone in 36%. Twenty-two (9.7%) patients aged 71.7 ± 14 died. A Charlson comorbidity index > 3, heart failure and connection to invasive mechanical ventilation were independent risk factors for death. An age > 65 years alone and other comorbidities were not risk factors. CONCLUSIONS: Viral pneumonia is the main cause of hospitalization for COVID-19, usually extensive and bilateral. The greater severity and poor prognosis of these patients are mainly related to comorbidities.

Diferencias y similitudes clínicas y epidemiológicas de la neumonía viral en dos pandemias / Clinical and epidemiological differences and similarities of viral pneumonias in two pandemics

BACKGROUND: In a decade, we faced two pandemic viruses, influenza A H1N1pdm09 and SARS CoV-2, whose most serious manifestation is pneumonia. AIM: To compare the clinical, epidemiological and management aspects of pneumonias caused by each pandemic virus in adults requiring hospitalization. Material and Methods: Comparative, observational study carried out at a regional Chilean hospital, including 75 patients with influenza A H1N1pdm09 prospectively studied in 2009 and 142 patients with SARS-CoV-2 studied in 2020. RESULTS: Patients with SARS-CoV-2 pneumonia were older (56 and 39.7 years respectively, p < 0.01) and had significantly more comorbidities. Cough, fever and myalgias were more frequent in influenza. Dyspnea was more frequent in COVID-19. Patients with COVID-19 had more extensive lung involvement and a longer hospitalization (13.6 and 8.6 days respectively, p = 0.01). There was no difference on ICU admission requirements and mortality attributable to pneumonia. Patients with influenza had greater APACHE scores and a higher frequency of a PaO2/FiO2 ratio ≤ 200. During COVID-19pandemic chest sean replaced x-ray examination. Also high-flow nasal cannulas and awake prone position ventilation were added as treatments. Conclusions: COVID-19 patients were older, had fewer classic flu symptoms but more dyspnea and longer hospitalization periods than patients with influenza.

[Bacteremic pneumococcal pneumonia in adults admitted to a general hospital. Experience in 60 cases]. / Neumonía neumocócica bacteriémica en adultos en hospital regional de Chile.

BACKGROUND: Bacteremic pneumococcal pneumonia (BPP) is a preventable disease with high morbimortality. AIM: To evaluate clinical aspects and mortality on BPP patients admitted to a Chilean regional hospital. PATIENTS AND METHODS: We looked for adult patients with Streptococcus pneumoniae isolated from blood cultures between 2010 and 2014 years and reviewed clinical records of those who were admitted with pneumonia. RESULTS: We identified 70 BPP patients: 58% were men, mean age was 56 years, 30% were > 65 years, 70% with basic public health insurance, 26% were alcoholics, 86% had comorbidities. Only two patients were vaccinated against S. pneumoniae. CURB-65 severity index for community acquired pneumonia was > 3 in 37% of patients. Twenty-four patients were admitted to ICU, twenty required mechanical ventilation and twenty-four died (34%). Mortality was associated with an age over 65 years, presence of comorbidities and complications of pneumonia. A total of 22 serotypes of S. pneumoniae were identified, five of them (1,3,7F,14 y 9V) were present in 57% of cases. CONCLUSIONS: Elevated mortality of our BNN patients was associated with comorbidities and possibly with socio economic factors, which conditioned a late access to medical care.

Impacto de la tuberculosis en el hospital de Puerto Montt / Impact of tuberculosis in Puerto Montt hospital, Chile

Resumen Objetivo: Dimensionar la demanda de atención y/u hospitalización de la tuberculosis (TBC) en el Hospital de Puerto Montt (HPM). Método: Revisión retrospectiva de los registros de TBC del Servicio de Salud del Reloncaví (SSDR) y del HPM entre los años 2011 y 2015. Se incluyeron todos los casos de TBC activa vistos en forma ambulatoria u hospitalizada en el HPM. Resultados: Se diagnosticaron en el SSDR 298 casos de TBC, y de ellos un 64% (192/298) fue pesquisado en el HPM. Se presentan datos socioeconómicos, epidemiológicos, clínicos, de laboratorio y forma de diagnóstico de 180 casos, que cumplieron criterios de inclusión: varones 62%, edad media 44 ± 19 años. El 72% correspondieron al estrato social de menores ingresos, 4% indigentes, solo 14% poseía enseñanza media completa, 11% analfabetos, ruralidad 19%. Las principales co-morbilidades fueron alcoholismo (17%), VIH (12%), Diabetes (10%). En aquellos con TBC pulmonar o pleural (128) el tiempo con síntomas con frecuencia era prolongado (15% > 90 días) y la radiología mostraba enfermedad avanzada: infiltrados bilaterales 73%, compromiso > 3 lóbulos 55%, una o más cavitaciones 34%. Se hospitalizó el 71% (126/180), 50% por necesidad de estudio, 48%por gravedad. El 8% necesitó Unidad de Paciente Crítico (UPC). Fallecieron 24 pacientes (13%). Se asoció significativamente a mortalidad el analfabetismo y necesidad de UPC. Conclusiones: En el SSDR la TBC es un problema sanitario que afecta principalmente a poblaciones más pobres y vulnerables.

Backgroud: Tuberculosis (TB) is still a problem that impacts on hospitals of high complexity. Aim: To assess demand for care and/or hospitalization because of TB in Puerto Montt Hospital (PMH), located in the southern of Chile. Patients and Methods: Retrospective study of all Reloncaví Health Service (RHS) and PMH clinical records, between 2011 and 2015. We include all ambulatory or hospitalized cases of active TB registered in PMH during the period of the study. Results: In RHS there were 298 cases of TB and 64% of them (192/298) was detected in HPM. We present social, economic, epidemiological, clinical, laboratory studies, and specific type of diagnosis of 180 cases that met inclusion criteria: men 62%, mean age 45 ± 19 years-old. The population with lower income was 72%, 4% homeless, 14% with complete high school, 11% illiterate and 19% lived at country side. Main co-morbidities were alcoholism 17%, HIV 12%, Diabetes Mellitus 10%. In the specific group of lung/pleural TB (128 cases) the time with symptoms was often prolonged (15% > 90 days) and imagen studies showed advanced pathology: bilateral infiltrates 73%>, affecting three or more lobes 55%, cavitations 34%. 71% (126/180) were hospitalized, because of necessity of more study (50%) or severity (48%), 8% required to enter to the Critical Care Unit (CCU). Twenty-four patients died (13%). Illiteracy and the need for CCU were associated with mortality. Conclusions: In RHS TB is a sanitary problem that affects principally the most poor and vulnerable populations.

Neumonía neumocócica bacteriémica en adultos en hospital regional de Chile / Bacteremic pneumococcal pneumonia in adults admitted to a general hospital: experience in 60 cases

Background: Bacteremic pneumococcal pneumonia (BPP) is a preventable disease with high morbimortality. Aim: To evaluate clinical aspects and mortality on BPP patients admitted to a Chilean regional hospital. Patients and Methods: We looked for adult patients with Streptococcus pneumoniae isolated from blood cultures between 2010 and 2014 years and reviewed clinical records of those who were admitted with pneumonia. Results: We identified 70 BPP patients: 58% were men, mean age was 56 years, 30% were > 65 years, 70% with basic public health insurance, 26% were alcoholics, 86% had comorbidities. Only two patients were vaccinated against S. pneumoniae. CURB-65 severity index for community acquired pneumonia was > 3 in 37% of patients. Twenty-four patients were admitted to ICU, twenty required mechanical ventilation and twenty-four died (34%). Mortality was associated with an age over 65 years, presence of comorbidities and complications of pneumonia. A total of 22 serotypes of S. pneumoniae were identified, five of them (1,3,7F,14 y 9V) were present in 57% of cases. Conclusions: Elevated mortality of our BNN patients was associated with comorbidities and possibly with socio economic factors, which conditioned a late access to medical care.

[Clinical impact of pandemic influenza A H1N1 in a Chilean regional hospital]. / Impacto clínico de la influenza A H1N1 pandémica en el hospital de Puerto Montt, Chile.

BACKGROUND: Pandemic flu (H1N1 ) strongly affected southern Chile during 2009. AIM: To report the logistic and organizational changes implemented at a regional hospital to face the pandemic. MATERIAL AND METHODS: All patients with flu like disease that were hospitalized, were prospectively enrolled at the Puerto Montt hospital. A nasopharyngeal aspirate was obtained in all for influenza virus A and B direct immunofluorescence and polymerase chain reaction (PCR). All epidemiological and clinical data of patients were recorded. RESULTS: Between May 29 and July 7, 2009, 184 adults were admitted to the hospital and in 117 patients aged 41 ± 18 years (56% females ), direct immunofluorescence was positive for influenza. In 67 of these patients PCR did not confirm the disease. These unconfirmed patients had a mean age of 49 ± 19 years (p < 0.01, compared with confirmed cases) and had a lower frequency of fever, rhinorrhea and chills. No significant differences in the incidence of community acquired pneumonia or chest X ray findings were observed between confirmed and unconfirmed cases. Hospital stay was over 15 days in 14% of confirmed cases and 5% of unconfirmed cases (p = 0.03). Fifteen patients, aged 53 ± 18 years, died. CONCLUSIONS: Low sensibility of direct immunofluorescence and delay in obtaining PCR confirmation of influenza posed a problem for the management of these patients.

Impacto clínico de la influenza A H1N1 pandémica en el hospital de Puerto Montt, Chile / Clinical impact of pandemic influenza A H1N1 in a Chilean regional hospital

Background: Pandemic flu (H1N1 ) strongly affected southern Chile during2009. Aim: To report the logistic and organizational changes implemented at a regional hospital to face the pandemic. Material and Methods: All patients with flu like disease that were hospitalized, were prospectively enrolled at the Puerto Montt hospital. A nasopharyngeal aspirate was obtained in all for influenza virus A and B direct immunofluorescence and polymerase chain reaction (PCR). All epidemiological and clinical data of patients were recorded. Results: Between May 29 and July 7, 2009, 184 adults were admitted to the hospital and in 117patients aged 41 ± 18 years (56 percent females ), direct immunofluorescence was positive for influenza. In 67 of these patients PCR did not confirm the disease. These unconfirmed patients had a mean age of 49 ± 19 years (p < 0.01, compared with confirmed cases) and had a lower frequency of fever, rhinorrhea and chills. No significant differences in the incidence of community acquired pneumonia or chest X ray findings were observed between confirmed and unconfirmed cases. Hospital stay was over 15 days in 14 percent of confirmed cases and 5 percent of unconfirmed cases (p = 0.03). Fifteen patients, aged 53 ± 18 years, died. Conclusions: Low sensibility of direct immunofluorescence and delay in obtaining PCR confirmation of influenza posed a problem for the management of these patients.

Papanicolaou: frotis sin componente endocervical / Papanicolaou: quality of the cervical samples

Objetivo: Evaluar la calidad de la toma del Papanicolaou (PAP) informados como frotis menos que óptimos (I-G7) en 2002 (sin componente endocervical), y conocer el seguimiento de las mujeres en el resultado del PAP siguiente 2003 - 2005. Método: Estudio descriptivo, cuantitativo y de seguimiento de cohorte. Se incluyó el resultado de 42.281 frotis de citología cervical, que correspondieron al universo de los PAP recolectados en 2002 en los consultorios de Atención Primaria de Salud del Área Metropolitana Sur de Santiago. Posteriormente, fueron seleccionados todos los PAP I-G7 de una cohorte de mujeres entre 25 a 50 años y sin antecedentes de lesiones o procedimientos cervicales. Resultados: El estudio evidenció que la toma de muestra de PAP en los consultorios, a excepción de 2 establecimientos, está dentro de los índices de calidad preconizados por el Ministerio de Salud. En el seguimiento de la cohorte de mujeres con PAP I-G7, se pesquisó la existencia de lesión cervical en un 3,38 por ciento de las mujeres que se repitieron el examen. Conclusión: Los PAP informados como frotis sin componente endocervical constituyen una categoría de riesgo, ya que el seguimiento de esas mujeres que se repitieron el examen de PAP en un período de hasta 3 años se detectaron lesiones cervicales de alto grado.

Objective: To evaluate the quality of sampling cervical cytological through the Papanicolaou (PAP) reported as less than optimal smears (I-G7), i.e. without endocervical component in theyear2002. To know the follow up of a women cohort, in the next PAP smears between 2003 to 2005. Method: Descriptive study, quantitative and follow up of a cohort. It included the results from 42.281 smears cervical cytological according to the national classification, which corresponded to the universe of PAP collected in the 2002 at clinics Primary Health Care in the South Metropolitan Area of Santiago. All PAP with outcome I-G7 from a cohort of women between 25 to 50 years and without history of injury or cervical procedures were selected. In addition, it was identified the clinics provenance. Results: The study showed that the sample of PAP in the clinics, with the exception of 2 establishments, it is within the quality indices expected by the Ministry of Health. In the follow-up of the cohort of women with PAP I-G7 was detected the existence of a cervical lesion 3.38 percent of the women who were repeated this smear. Conclusion: PAP smears reported as without component endocervical constitute a category of risk, since the follow up the women who were repeated this PAP smear over a period of up to 3 years high-grade cervical lesions were detected.