Beneficios de los bloqueos analgésicos, PENG (PEricapsular Nerve Group), en la recuperación precoz tras la cirugía de cadera / Benefits of analgesic blocks, PENG block (PEricapsular Nerve Group), in fast recovery after hip surgery

Introducción: La fractura de cadera es una emergencia ortopédica frecuente que asocia elevada morbimortalidad y dolor intenso. Las técnicas analgo-anestésicas locorregionales, tanto centrales como periféricas, ocupan un lugar preferente dentro del arsenal terapéutico multimodal. A los bloqueos clásicos se ha sumado recientemente el bloqueo pericapsular, o PENG (PEricapsular Nerve Group). El objetivo es evaluar en pacientes con fractura de cadera la eficacia antinociceptiva del bloqueo PENG preoperatorio, el bloqueo motor residual y el tiempo necesario para la recuperación funcional postoperatoria. Material y métodos: Estudio observacional descriptivo prospectivo en pacientes programados para artroplastia total de cadera. El bloqueo PENG se realizó previo a la cirugía. Se evaluó el dolor con escala visual numérica (EVN) antes de la realización del bloqueo, 30minutos después, en el postoperatorio inmediato y a las 24horas de la intervención, el grado de bloqueo motor según la escala de Bromage y el tiempo necesario para la deambulación asistida. Resultados: En todos los pacientes el bloqueo PENG proporcionó analgesia eficaz. Logró disminuir 3 o más puntos la EVN en todos los momentos evaluados. La diferencia media entre el dolor previo y posterior al bloqueo fue de 7,5 puntos en la EVN, lo que permitió el traslado y la colocación del paciente sin alteración hemodinámica, exacerbación del dolor, ni otras complicaciones. Conclusiones: El bloqueo PENG es una técnica analgésica regional efectiva y segura para pacientes con fractura de cadera; facilita la movilización y la colocación previa a la cirugía sin exacerbación del dolor, y favorece una temprana movilidad y rehabilitación.

Introduction: Hip fracture is a frequent orthopedic emergency which associates high morbidity and mortality and intense pain. Locoregional analgo-anesthetic techniques, both central and peripheral, occupy a preferential place in the multimodal therapeutic arsenal. Recently, a new regional blockade has emerged, the pericapsular block or PENG block (PEricapsular Nerve Group). The objective is to evaluate in patients with hip fracture, the antinociceptive efficacy of the preoperative PENG block, residual motor block and time for postoperative functional recovery. Method and materials: Prospective descriptive observational study with patients going to have total hip arthroplasty. PENG block was performed before surgery. Pain was assessed with the Visual Numerical Scale (VNS) before the blockade, 30min later, in the immediate postoperative period and 24h after the intervention. Motor block according to the Bromage scale and time needed for assisted walking were also evaluated. Results: PENG block provided effective analgesia in all patients, with a decrease in at least 3 points on the VNS at every step in which it was evaluated. The average difference between pain before and after the block was 7.5 points on the VNS. It allowed the transfer and placement of the patient without hemodynamic alteration, exacerbation of pain or other complications. Conclusions: PENG block is an effective and safe regional analgesic technique for patients with hip fracture. It allows mobilization and placement before surgery without pain exacerbation, promoting early mobility and rehabilitation.(AU)

[Translated article] Benefits of analgesic blocks, PENG block (PEricapsular Nerve Group), in fast recovery after hip surgery / Beneficios de los bloqueos analgésicos, PENG (PEricapsular Nerve Group), en la recuperación precoz tras la cirugía de cadera

Introduction: Hip fracture is a frequent orthopedic emergency which associates high morbidity and mortality and intense pain. Locoregional analgo-anesthetic techniques, both central and peripheral, occupy a preferential place in the multimodal therapeutic arsenal. Recently, a new regional blockade has emerged, the pericapsular block or PENG block (PEricapsular Nerve Group). The objective is to evaluate in patients with hip fracture, the antinociceptive efficacy of the preoperative PENG block, residual motor block and time for postoperative functional recovery. Method and materials: Prospective descriptive observational study with patients going to have total hip arthroplasty. PENG block was performed before surgery. Pain was assessed with the Visual Numerical Scale (VNS) before the blockade, 30min later, in the immediate postoperative period and 24h after the intervention. Motor block according to the Bromage scale and time needed for assisted walking were also evaluated. Results: PENG block provided effective analgesia in all patients, with a decrease in at least 3 points on the VNS at every step in which it was evaluated. The average difference between pain before and after the block was 7.5 points on the VNS. It allowed the transfer and placement of the patient without hemodynamic alteration, exacerbation of pain or other complications. Conclusions: PENG block is an effective and safe regional analgesic technique for patients with hip fracture. It allows mobilization and placement before surgery without pain exacerbation, promoting early mobility and rehabilitation.(AU)

Introducción: La fractura de cadera es una emergencia ortopédica frecuente que asocia elevada morbimortalidad y dolor intenso. Las técnicas analgo-anestésicas locorregionales, tanto centrales como periféricas, ocupan un lugar preferente dentro del arsenal terapéutico multimodal. A los bloqueos clásicos se ha sumado recientemente el bloqueo pericapsular, o PENG (PEricapsular Nerve Group). El objetivo es evaluar en pacientes con fractura de cadera la eficacia antinociceptiva del bloqueo PENG preoperatorio, el bloqueo motor residual y el tiempo necesario para la recuperación funcional postoperatoria. Material y métodos: Estudio observacional descriptivo prospectivo en pacientes programados para artroplastia total de cadera. El bloqueo PENG se realizó previo a la cirugía. Se evaluó el dolor con escala visual numérica (EVN) antes de la realización del bloqueo, 30minutos después, en el postoperatorio inmediato y a las 24horas de la intervención, el grado de bloqueo motor según la escala de Bromage y el tiempo necesario para la deambulación asistida. Resultados: En todos los pacientes el bloqueo PENG proporcionó analgesia eficaz. Logró disminuir 3 o más puntos la EVN en todos los momentos evaluados. La diferencia media entre el dolor previo y posterior al bloqueo fue de 7,5 puntos en la EVN, lo que permitió el traslado y la colocación del paciente sin alteración hemodinámica, exacerbación del dolor, ni otras complicaciones. Conclusiones: El bloqueo PENG es una técnica analgésica regional efectiva y segura para pacientes con fractura de cadera; facilita la movilización y la colocación previa a la cirugía sin exacerbación del dolor, y favorece una temprana movilidad y rehabilitación.

Benefits of analgesic blocks, PENG block (PEricapsular Nerve Group), in fast recovery after hip surgery. / Beneficios de los bloqueos analgésicos, PENG (PEricapsular Nerve Group), en la recuperación precoz tras la cirugía de cadera.

INTRODUCTION: Hip fracture is a frequent orthopedic emergency which associates high morbidity and mortality and intense pain. Locoregional analgo-anesthetic techniques, both central and peripheral, occupy a preferential place in the multimodal therapeutic arsenal. Recently, a new regional blockade has emerged, the pericapsular block or PENG block (PEricapsular Nerve Group). The objective is to evaluate in patients with hip fracture, the antinociceptive efficacy of the preoperative PENG block, residual motor block and time for postoperative functional recovery. METHOD AND MATERIALS: Prospective descriptive observational study with patients going to have total hip arthroplasty. PENG block was performed before surgery. Pain was assessed with the Visual Numerical Scale (VNS) before the blockade, 30min later, in the immediate postoperative period and 24h after the intervention. Motor block according to the Bromage scale and time needed for assisted walking were also evaluated. RESULTS: PENG block provided effective analgesia in all patients, with a decrease in at least 3 points on the VNS at every step in which it was evaluated. The average difference between pain before and after the block was 7.5 points on the VNS. It allowed the transfer and placement of the patient without hemodynamic alteration, exacerbation of pain or other complications. CONCLUSIONS: PENG block is an effective and safe regional analgesic technique for patients with hip fracture. It allows mobilization and placement before surgery without pain exacerbation, promoting early mobility and rehabilitation.

Stereotactic Body Radiotherapy for Kidney Cancer: Ready for Prime Time?

The standard treatment for renal cell carcinoma (RCC) is surgery. However, a number of patients will not be candidates for surgical treatment or will reject this therapeutic approach. Therefore, alternative approaches are required. Historically, radiotherapy has been considered an ineffective treatment for RCC due to the radioresistance of renal tumour cells to conventional fractionation and the increased rate of toxicity. Stereotactic body radiotherapy (SBRT) is a radiotherapy technique that provides a non-invasive ablative treatment with remarkable rates of local control in both primary tumours and metastases in several locations, with a low associated morbidity due to the highly conformal dose and the use of image-guided techniques. Current evidence shows that a higher dose per fraction, achieving a higher biological effective dose, can overcome the radioresistance of RCC cells. Therefore, SBRT, as well as the combination of SBRT and new emerging immune therapies, has a potential role in the local treatment of primary RCC and oligometastatic RCC patients.

[Translated article] Benefits of analgesic blocks, PENG block (PEricapsular Nerve Group), in fast recovery after hip surgery.

INTRODUCTION: Hip fracture is a frequent orthopaedic emergency which associates high morbidity and mortality and intense pain. Locoregional analgo-anaesthetic techniques, both central and peripheral, occupy a preferential place in the multimodal therapeutic arsenal. Recently, a new regional blockade has emerged, the pericapsular block or PENG block (PEricapsular Nerve Group). The objective is to evaluate in patients with hip fracture, the antinociceptive efficacy of the preoperative PENG block, residual motor block and time for postoperative functional recovery. METHOD AND MATERIALS: Prospective descriptive observational study with patients going to have total hip arthroplasty. PENG block was performed before surgery. Pain was assessed with the Visual Numerical Scale (VNS) before the blockade, 30min later, in the immediate postoperative period and 24h after the intervention. Motor block according to the Bromage scale and time needed for assisted walking were also evaluated. RESULTS: PENG block provided effective analgesia in all patients, with a decrease in at least 3 points on the VNS at every step in which it was evaluated. The average difference between pain before and after the block was 7.5 points on the VNS. It allowed the transfer and placement of the patient without haemodynamic alteration, exacerbation of pain or other complications. CONCLUSIONS: PENG block is an effective and safe regional analgesic technique for patients with hip fracture. It allows mobilisation and placement before surgery without pain exacerbation, promoting early mobility and rehabilitation.

Predictive factors of six-week mortality in critically ill patients with SARS-CoV-2: A multicenter prospective study.

OBJECTIVE: The objective of the study is to identify the risk factors associated with mortality at six weeks, especially by analyzing the role of antivirals and munomodulators. DESIGN: Prospective descriptive multicenter cohort study. SETTING: 26 Intensive care units (ICU) from Andalusian region in Spain. PATIENTS OR PARTICIPANTS: Consecutive critically ill patients with confirmed SARS-CoV-2 infection were included from March 8 to May 30. INTERVENTIONS: None. VARIABLES: Variables analyzed were demographic, severity scores and clinical condition. Support therapy, drug and mortality were analyzed. An univariate followed by multivariate Cox regression with propensity score analysis was applied. RESULTS: 495 patients were enrolled, but 73 of them were excluded for incomplete data. Thus, 422 patients were included in the final analysis. Median age was 63 years and 305 (72.3%) were men. ICU mortality: 144/422 34%; 14 days mortality: 81/422 (19.2%); 28 days mortality: 121/422 (28.7%); 6-week mortality 152/422 36.5%. By multivariable Cox proportional analysis, factors independently associated with 42-day mortality were age, APACHE II score, SOFA score at ICU admission >6, Lactate dehydrogenase at ICU admission >470U/L, Use of vasopressors, extrarenal depuration, %lymphocytes 72h post-ICU admission <6.5%, and thrombocytopenia whereas the use of lopinavir/ritonavir was a protective factor. CONCLUSION: Age, APACHE II, SOFA>value of 6 points, along with vasopressor requirements or renal replacement therapy have been identified as predictor factors of mortality at six weeks. Administration of corticosteroids showed no benefits in mortality, as did treatment with tocilizumab. Lopinavir/ritonavir administration is identified as a protective factor.

Stereotactic body radiotherapy for early-stage non-small cell lung cancer: a multicentre study by the Oncologic Group for the Study of Lung Cancer (Spanish Radiation Oncology Society).

PURPOSE/OBJECTIVE(S): Stereotactic body radiotherapy (SBRT) has become the standard of care for patients with medically inoperable early-stage non-small cell lung cancer (NSCLC) and for patients who refuse surgery. The aim of this study was to evaluate the effectiveness and safety of primary SBRT in patients with early-stage NSCLC. MATERIALS/METHODS: Retrospective multicenter study of 397 patients (416 primary lung tumours) treated with SBRT at 18 centres in Spain. 83.2% were men. The median age was 74.4 years. In 94.4% of cases, the tumour was inoperable. The pathological report was available in 54.6% of cases. SPSS vs 22.0. was used to perform all statistical analyses. RESULTS: Complete response was obtained in 53.6% of cases. Significant prognostic factors were standard CT planning (p = 0.014) and 4D cone beam CT (p = 0.000). Acute and chronic toxicity ≥ grade 3 was observed in 1.2% of cases. At a median follow-up of 30 months, local relapse was 9.6%, lymph node relapse 12.8%, distant metastasis 16.6%, and another lung tumour 11.5%. Complete response was the only significant prognostic factor for local relapse (p = 0.012) and distant metastasis (p = 0.001). The local relapse-free survival was 88.7%. The overall survival was 75.7%. The cancer-specific survival was 92.7%. The disease-free survival was 78.7%. CONCLUSION: SBRT is an effective and well-tolerated treatment option for patients with early-stage lung cancer who are not suitable for surgery. The most important prognostic factor for local and distant recurrence was complete response, which in our sample depended on the type of CT planning and the IGRT technique.

Antiproliferative, genotoxic and mutagenic potential of synthetic chocolate food flavoring / Potencial antiproliferativo, genotóxico e mutagênico do aroma de chocolate sintético para alimentos

Flavoring additives are of great technological importance for the food industry. However, there is little information regarding the toxicological properties of these micro-ingredients, especially at the cellular level. The present study used meristematic root cells of Allium cepa L. to evaluate the toxicity of a liquid, aroma and flavor synthetic chocolate additive, manufactured and widely marketed throughout Brazil and exported to other countries in South America. The flavoring concentrations evaluated were 100.00; 50.00; 25.00; 1.00; 0.50 and 0.25 µL/L, where the highest concentration established was one-hundred times lower than that commercially suggested for use. The concentration 100 µL/L substantially reduced cell division of meristems within 24- and 48-hours exposure. Concentrations from 100.00 to 0.50 µL/L resulted in a significant number of prophases to the detriment of the other phases of cell division, indicating an aneugenic activity, and induced a significant number of cellular changes, with emphasis on micronuclei, nuclear buds and chromosomal breaks. Under the established analysis conditions, with the exception of concentration 0.25 µL/L, the flavoring of chocolate caused cytotoxicity, genotoxicity and mutagenicity to root meristems.

Os aditivos aromatizantes têm grande importância tecnológica para a indústria de alimentos. Contudo, poucas são as informações quanto as propriedades toxicológicas desses microingredientes, especialmente, em nível celular. No presente estudo avaliou-se, sobre as células meristemáticas de raízes de Allium cepa L., a toxicidade de um aditivo sintético líquido de aroma e sabor de chocolate, fabricado e amplamente comercializado em todo Brasil, e exportado para outros países da América do Sul. As concentrações de aromatizante avaliadas foram 100,00; 50,00; 25,00; 1,00; 0,50 e 0,25 µL/L, onde a maior concentração estabelecida foi cem vezes menor que a sugerida comercialmente para uso. Com base na interpretação dos resultados, a concentração 100 µL/L reduziu substancialmente a divisão celular dos meristemas nas 24 e 48 horas de exposição. As concentrações 100,00 a 0,50 µL/L demonstraram número significativo de prófases em detrimento as outras fases da divisão celular, indicando ação aneugênica, e induziram número significativo de alterações celulares, com ênfase a micronúcleos, broto nucleares e quebras cromossômicas. Nas condições de análises estabelecidas, com exceção a concentração 0,25 µL/L, o aromatizante de chocolate causou citotoxicidade, genotoxicidade e mutagenicidade aos meristemas radiculares.

Antiproliferative, genotoxic and mutagenic potential of synthetic chocolate food flavoring

Abstract Flavoring additives are of great technological importance for the food industry. However, there is little information regarding the toxicological properties of these micro-ingredients, especially at the cellular level. The present study used meristematic root cells of Allium cepa L. to evaluate the toxicity of a liquid, aroma and flavor synthetic chocolate additive, manufactured and widely marketed throughout Brazil and exported to other countries in South America. The flavoring concentrations evaluated were 100.00; 50.00; 25.00; 1.00; 0.50 and 0.25 µL/L, where the highest concentration established was one-hundred times lower than that commercially suggested for use. The concentration 100 µL/L substantially reduced cell division of meristems within 24- and 48-hours exposure. Concentrations from 100.00 to 0.50 µL/L resulted in a significant number of prophases to the detriment of the other phases of cell division, indicating an aneugenic activity, and induced a significant number of cellular changes, with emphasis on micronuclei, nuclear buds and chromosomal breaks. Under the established analysis conditions, with the exception of concentration 0.25 µL/L, the flavoring of chocolate caused cytotoxicity, genotoxicity and mutagenicity to root meristems.

Resumo Os aditivos aromatizantes têm grande importância tecnológica para a indústria de alimentos. Contudo, poucas são as informações quanto as propriedades toxicológicas desses microingredientes, especialmente, em nível celular. No presente estudo avaliou-se, sobre as células meristemáticas de raízes de Allium cepa L., a toxicidade de um aditivo sintético líquido de aroma e sabor de chocolate, fabricado e amplamente comercializado em todo Brasil, e exportado para outros países da América do Sul. As concentrações de aromatizante avaliadas foram 100,00; 50,00; 25,00; 1,00; 0,50 e 0,25 µL/L, onde a maior concentração estabelecida foi cem vezes menor que a sugerida comercialmente para uso. Com base na interpretação dos resultados, a concentração 100 µL/L reduziu substancialmente a divisão celular dos meristemas nas 24 e 48 horas de exposição. As concentrações 100,00 a 0,50 µL/L demonstraram número significativo de prófases em detrimento as outras fases da divisão celular, indicando ação aneugênica, e induziram número significativo de alterações celulares, com ênfase a micronúcleos, broto nucleares e quebras cromossômicas. Nas condições de análises estabelecidas, com exceção a concentração 0,25 µL/L, o aromatizante de chocolate causou citotoxicidade, genotoxicidade e mutagenicidade aos meristemas radiculares.

Antiproliferative, genotoxic and mutagenic potential of synthetic chocolate food flavoring / Potencial antiproliferativo, genotóxico e mutagênico do aroma de chocolate sintético para alimentos

Flavoring additives are of great technological importance for the food industry. However, there is little information regarding the toxicological properties of these micro-ingredients, especially at the cellular level. The present study used meristematic root cells of Allium cepa L. to evaluate the toxicity of a liquid, aroma and flavor synthetic chocolate additive, manufactured and widely marketed throughout Brazil and exported to other countries in South America. The flavoring concentrations evaluated were 100.00; 50.00; 25.00; 1.00; 0.50 and 0.25 µL/L, where the highest concentration established was one-hundred times lower than that commercially suggested for use. The concentration 100 µL/L substantially reduced cell division of meristems within 24- and 48-hours exposure. Concentrations from 100.00 to 0.50 µL/L resulted in a significant number of prophases to the detriment of the other phases of cell division, indicating an aneugenic activity, and induced a significant number of cellular changes, with emphasis on micronuclei, nuclear buds and chromosomal breaks. Under the established analysis conditions, with the exception of concentration 0.25 µL/L, the flavoring of chocolate caused cytotoxicity, genotoxicity and mutagenicity to root meristems.

Os aditivos aromatizantes têm grande importância tecnológica para a indústria de alimentos. Contudo, poucas são as informações quanto as propriedades toxicológicas desses microingredientes, especialmente, em nível celular. No presente estudo avaliou-se, sobre as células meristemáticas de raízes de Allium cepa L., a toxicidade de um aditivo sintético líquido de aroma e sabor de chocolate, fabricado e amplamente comercializado em todo Brasil, e exportado para outros países da América do Sul. As concentrações de aromatizante avaliadas foram 100,00; 50,00; 25,00; 1,00; 0,50 e 0,25 µL/L, onde a maior concentração estabelecida foi cem vezes menor que a sugerida comercialmente para uso. Com base na interpretação dos resultados, a concentração 100 µL/L reduziu substancialmente a divisão celular dos meristemas nas 24 e 48 horas de exposição. As concentrações 100,00 a 0,50 µL/L demonstraram número significativo de prófases em detrimento as outras fases da divisão celular, indicando ação aneugênica, e induziram número significativo de alterações celulares, com ênfase a micronúcleos, broto nucleares e quebras cromossômicas. Nas condições de análises estabelecidas, com exceção a concentração 0,25 µL/L, o aromatizante de chocolate causou citotoxicidade, genotoxicidade e mutagenicidade aos meristemas radiculares.

Anesthetic considerations for functional endoscopic sinus surgery in a patient with Kartagener syndrome.

Kartagener's syndrome (KS) is a rare genetic disease characterised by the triad of sinusitis, bronchiectasis, and situs inversus. This syndrome is associated with an increased risk of respiratory complications. Therefore, both the anaesthetic technique and the agents used must be carefully chosen according to the type of intervention and the patient's baseline condition. We present the case of a 48-year-old woman with KS, scheduled for functional endoscopic sinus surgery (FESS) and septoplasty under general anaesthesia. The main anaesthetic considerations in patients with KS are related to anatomical variations, pulmonary and cardiac functions, and respiratory infections. In this case, measures that reduce perioperative complications in KS are reviewed together with the special anaesthetic management in FESS, derived primarily from the need to maintain a bloodless surgical field and the use of induced hypotension techniques.

Antiproliferative, genotoxic and mutagenic potential of synthetic chocolate food flavoring.

Flavoring additives are of great technological importance for the food industry. However, there is little information regarding the toxicological properties of these micro-ingredients, especially at the cellular level. The present study used meristematic root cells of Allium cepa L. to evaluate the toxicity of a liquid, aroma and flavor synthetic chocolate additive, manufactured and widely marketed throughout Brazil and exported to other countries in South America. The flavoring concentrations evaluated were 100.00; 50.00; 25.00; 1.00; 0.50 and 0.25 µL/L, where the highest concentration established was one-hundred times lower than that commercially suggested for use. The concentration 100 µL/L substantially reduced cell division of meristems within 24- and 48-hours exposure. Concentrations from 100.00 to 0.50 µL/L resulted in a significant number of prophases to the detriment of the other phases of cell division, indicating an aneugenic activity, and induced a significant number of cellular changes, with emphasis on micronuclei, nuclear buds and chromosomal breaks. Under the established analysis conditions, with the exception of concentration 0.25 µL/L, the flavoring of chocolate caused cytotoxicity, genotoxicity and mutagenicity to root meristems.

Anesthetic considerations for functional endoscopic sinus surgery in a patient with Kartagener syndrome. / Consideraciones anestésicas para cirugía endoscópica nasosinusal en una paciente con síndrome de Kartagener.

Kartagener's syndrome (KS) is a rare genetic disease characterized by the triad of sinusitis, bronchiectasis, and situs inversus. This syndrome is associated with an increased risk of respiratory complications. Therefore, both the anesthetic technique and the agents used must be carefully chosen according to the type of intervention and the patient's baseline condition. We present the case of a 48-year-old woman with KS, scheduled for functional endoscopic sinus surgery (FESS) and septoplasty under general anesthesia. The main anesthetic considerations in patients with KS are related to anatomical variations, pulmonary and cardiac functions, and respiratory infections. In this case, measures that reduce perioperative complications in KS are reviewed together with the special anesthetic management in FESS, derived primarily from the need to maintain a bloodless surgical field and the use of induced hypotension techniques.

Predictive factors of six-week mortality in critically ill patients with SARS-CoV-2: A multicenter prospective study.

OBJECTIVE: The objective of the study is to identify the risk factors associated with mortality at six weeks, especially by analyzing the role of antivirals and munomodulators. DESIGN: Prospective descriptive multicenter cohort study. SETTING: 26 Intensive care units (ICU) from Andalusian region in Spain. PATIENTS OR PARTICIPANTS: Consecutive critically ill patients with confirmed SARS-CoV-2 infection were included from March 8 to May 30. INTERVENTIONS: None. VARIABLES: Variables analyzed were demographic, severity scores and clinical condition. Support therapy, drug and mortality were analyzed. An univariate followed by multivariate Cox regression with propensity score analysis was applied. RESULTS: 495 patients were enrolled, but 73 of them were excluded for incomplete data. Thus, 422 patients were included in the final analysis. Median age was 63 years and 305 (72.3%) were men. ICU mortality: 144/422 34%; 14 days mortality: 81/422 (19.2%); 28 days mortality: 121/422 (28.7%); 6-week mortality 152/422 36.5%. By multivariable Cox proportional analysis, factors independently associated with 42-day mortality were age, APACHE II score, SOFA score at ICU admission >6, Lactate dehydrogenase at ICU admission >470U/L, Use of vasopressors, extrarenal depuration, %lymphocytes 72h post-ICU admission <6.5%, and thrombocytopenia whereas the use of lopinavir/ritonavir was a protective factor. CONCLUSION: Age, APACHE II, SOFA>value of 6 points, along with vasopressor requirements or renal replacement therapy have been identified as predictor factors of mortality at six weeks. Administration of corticosteroids showed no benefits in mortality, as did treatment with tocilizumab. Lopinavir/ritonavir administration is identified as a protective factor.

A one-arm surgical trial of obstructive sleep apnea (OSA) patients before and 12 months after Bilateral Internal Ramus Distraction of the mandible (BIRD).

BACKGROUND: An innovative approach for the primary and definitive treatment of obstructive sleep apnea (OSA) in adult patients is presented: Bilateral Internal Ramus Distraction of the mandible (BIRD), which is a slow, progressive and more stable procedure to advance the mandibular bone. This study investigated whether this surgical approach is useful to cure OSA. METHODS: Study design was of an interventional (surgical) one-arm trial of OSA patients assessed before and 12 months after BIRD. All patients were evaluated by pre- and post-operative polysomnography and three-dimensional scans. The amount of skeletal advancement, percentage of upper airway volume increase and postoperative value of mandibular occlusal plane were the predictor variables. Changes in the apnoea-hypopnoea index (AHI), oxygen desaturation index (ODI), and percentage of time with saturation under 90% (TC90) were the main outcome variables. FINDINGS: Thirty-two subjects with a mean ± SD age of 41.9 ± 13.3 years and 87.5% male were included, and they were followed-up 32 ± 14.2 months. AHI was 47.9 ± 23.1 per hour before surgery and the Epworth Sleepiness Scale (ESS) was 13.4 ± 4.4. Postoperative AHI was 4.8 ± 5.6 per hour 12 months after surgery (P < 0.001), with 81.2% of the patients considered cured (AHI<5) and 18.8% suffering from a mild-to-moderate residual OSA. ESS decreased to 1.9 ± 1.8 at the end of the surgical treatment (P < 0.001). 3D changes revealed an upper airway volume increase of 188.4% ± 73.5% (P < 0.001). INTERPRETATION: Lengthening the mandibular ramus by distraction osteogenesis to cure OSA appears to be more effective and safer when compared to other surgical protocols, especially in very severe cases with initial AHI>50/h. Titration of the mandibular advancement weekly using respiratory polygraphy allows better healing control and customization of the skeletal advancement, enhancing the aesthetic result.

Antiviral drugs targeting endosomal membrane proteins inhibit distant animal and human pathogenic viruses.

The endocytic pathway is a common strategy that several highly pathogenic viruses use to enter into the cell. To demonstrate the usefulness of this pathway as a common target for the development of broad-spectrum antivirals, the inhibitory effect of drug compounds targeting endosomal membrane proteins were investigated. This study entailed direct comparison of drug effectiveness against animal and human pathogenic viruses, namely Ebola (EBOV), African swine fever virus (ASFV), and the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). A panel of experimental and FDA-approved compounds targeting calcium channels and PIKfyve at the endosomal membrane caused potent reductions of entry up to 90% in SARS-CoV-2 S-protein pseudotyped retrovirus. Similar inhibition was observed against transduced EBOV glycoprotein pseudovirus and ASFV. SARS-CoV-2 infection was potently inhibited by selective estrogen receptor modulators in cells transduced with pseudovirus, among them Raloxifen inhibited ASFV with very low 50% inhibitory concentration. Finally, the mechanism of the inhibition caused by the latter in ASFV infection was analyzed. Overall, this work shows that cellular proteins related to the endocytic pathway can constitute suitable cellular targets for broad range antiviral compounds.

4-Deoxyphorbol inhibits HIV-1 infection in synergism with antiretroviral drugs and reactivates viral reservoirs through PKC/MEK activation synergizing with vorinostat.

Latent HIV reservoirs are the main obstacle to eradicate HIV infection. One strategy proposes to eliminate these viral reservoirs by pharmacologically reactivating the latently infected T cells. We show here that a 4-deoxyphorbol ester derivative isolated from Euphorbia amygdaloides ssp. semiperfoliata, 4ß-dPE A, reactivates HIV-1 from latency and could potentially contribute to decrease the viral reservoir. 4ß-dPE A shows two effects in the HIV replication cycle, infection inhibition and HIV transactivation, similarly to other phorboids PKC agonists such PMA and prostratin and to other diterpene esters such SJ23B. Our data suggest 4ß-dPE A is non-tumorigenic, unlike the related compound PMA. As the compounds are highly similar, the lack of tumorigenicity by 4ß-dPE A could be due to the lack of a long side lipophilic chain that is present in PMA. 4ß-dPE activates HIV transcription at nanomolar concentrations, lower than the concentration needed by other latency reversing agents (LRAs) such as prostratin and similar to bryostatin. PKCθ/MEK activation is required for the transcriptional activity, and thus, anti-latency activity of 4ß-dPE A. However, CD4, CXCR4 and CCR5 receptors down-regulation effect seems to be independent of PCK/MEK, suggesting the existence of at least two different targets for 4ß-dPE A. Furthermore, NF-κb transcription factor is involved in 4ß-dPE HIV reactivation, as previously shown for other PKCs agonists. We also studied the effects of 4ß-dPE A in combination with other LRAs. When 4ß-dPE A was combined with another PKC agonists such as prostratin an antagonic effect was achieved, while, when combined with an HDAC inhibitor such as vorinostat, a strong synergistic effect was obtained. Interestingly, the latency reversing effect of the combination was synergistically diminishing the EC50 value but also increasing the efficacy showed by the drugs alone. In addition, combinations of 4ß-dPE A with antiretroviral drugs as CCR5 antagonist, NRTIs, NNRTIs and PIs, showed a consistent synergistic effect, suggesting that the combination would not interefer with antiretroviral therapy (ART). Finally, 4ß-dPE A induced latent HIV reactivation in CD4 + T cells of infected patients under ART at similar levels than the tumorigenic phorbol derivative PMA, showing a clear reactivation effect. In summary, we describe here the mechanism of action of a new potent deoxyphorbol derivative as a latency reversing agent candidate to decrease the size of HIV reservoirs.

Geographic distribution of chronic obstructive pulmonary disease prevalence in Africa, Asia and Australasia.

OBJECTIVE: To visualise spatial data on chronic obstructive pulmonary disease (COPD) prevalence in Africa, Asia and Australasia using a Geographic Information System (GIS) inverse distance weighted (IDW) interpolation technique.DESIGN: Prevalence rates from population surveys on individuals aged ≥40, with spirometry-confirmed COPD, were searched systematically. The prevalence observed in 59 selected surveys and the geographic coordinates of the places where they were conducted informed a GIS computer programme. The prevalence was represented by an ascending chromatic scale (blue-green-yellow-orange-brown-red) in the GIS maps.RESULTS: IDW-interpolation GIS maps were obtained of all the geographic areas investigated, and even from regions lacking data. Areas of high/very high prevalence were found in: Southern Africa and in most of the Central and Eastern Africa regions; in practically all of Central Asia; in the western regions of Southern Asia; in the southern regions of the East European Plain and the West Siberian Plain of Northern Asia; and in the Malay Archipelago. Intermediate prevalence predominated in Oceania and in most of the other regions of Africa and Asia.CONCLUSION: Despite some biases inherent to the interpolation method used in the present study, our approach provided an understandable visual perspective of the COPD prevalence distribution in these geographic regions.