Physics and small-scale dosimetry of α $\alpha$ -emitters for targeted radionuclide therapy: The case of 211 At $

BACKGROUND: Monte Carlo simulations have been considered for a long time the gold standard for dose calculations in conventional radiotherapy and are currently being applied for the same purpose in innovative radiotherapy techniques such as targeted radionuclide therapy (TRT). PURPOSE: We present in this work a benchmarking study of the latest version of the Transport d'Ions Lourds Dans l'Aqua & Vivo (TILDA-V ) Monte Carlo track structure code, highlighting its capabilities for describing the full slowing down of α $\alpha$ -particles in water and the energy deposited in cells by α $\alpha$ -emitters in the context of TRT. METHODS: We performed radiation transport simulations of α $\alpha$ -particles (10 keV u - 1 ${\rm u}^{-1}$ -100 MeV u - 1 ${\rm u}^{-1}$ ) in water with TILDA-V and the Particle and Heavy Ion Transport code System (PHITS) version 3.33. We compared the predictions of each code in terms of track parameters (stopping power, range and radial dose profiles) and cellular S-values of the promising radionuclide astatine-211 ( 211 At $^{211}{\rm At}$ ). Additional comparisons were made with available data in the literature. RESULTS: The stopping power, range and radial dose profiles of α $\alpha$ -particles computed with TILDA-V were in excellent agreement with other calculations and available data. Overall, minor differences with PHITS were ascribed to phase effects, that is, related to the use of interaction cross sections computed for water vapor or liquid water. However, important discrepancies were observed in the radial dose profiles of monoenergetic α $\alpha$ -particles, for which PHITS results showed a large underestimation of the absorbed dose compared to other codes and experimental data. The cellular S-values of 211 At $^{211}{\rm At}$ computed with TILDA-V  agreed within 4% with the values predicted by PHITS and MIRDcell. CONCLUSIONS: The validation of the TILDA-V code presented in this work opens the possibility to use it as an accurate simulation tool for investigating the interaction of α $\alpha$ -particles in biological media down to the nanometer scale in the context of medical research. The code may help nuclear medicine physicians in their choice of α $\alpha$ -emitters for TRT. Further research will focus on the application of TILDA-V for quantifying radioinduced damage on the deoxyribonucleic acid (DNA) molecule.

An uncommon case of right hepatic duct entering cystic duct associated to multiple complications of biliary tract disease: acute pancreatitis, hepatolithiasis, acute cholecystitis and hepatic abscess.

Anatomical variations of the biliary tree pose diagnostic and treatment challenges. While most are harmless and often discovered incidentally during procedures, some can lead to clinical issues and biliary complications, making knowledge of these variants crucial to prevent surgical mishaps. Here, we present an unusual and clinically significant case. A 61-year-old man is admitted to the hospital with epigastric pain and diagnosis of pancreatitis of biliary origin and intermediate risk of choledocholithiasis. Magnetic resonance cholangiopancreatography (MRCP) reported hepatolithiasis and choledocholithiasis, whereas endoscopic retrograde cholangiopancreatography showed cystic drain of the right hepatic duct. One month later the patient presented again to the emergency room with increasing abdominal pain and a computed tomography that demonstrated the presence of hepatic abscess and acute cholecystitis. The patient underwent percutaneous drain abscess and a subtotal laparoscopic cholecystectomy. Biliary anatomical variants present challenges on the diagnostic investigations, interventional and surgical procedures, understanding the possible complications is essential.

Postoperative complications and predictors of mortality in patients with COVID-19.

BACKGROUND: There are limited data about the perioperative outcomes of coronavirus disease 2019 (COVID-19) patients that needed emergency general surgery. The aim of the present study was to describe the perioperative outcomes and mortality of patients with COVID-19 who underwent emergency surgery. MATERIALS AND METHODs: Retrospective study of COVID-19 patients symptomatic versus asymptomatic from March 2020 to February 2022 that needed an emergency surgery in a national referral hospital. RESULTS: Forty-four patients were included in this study. Patients with symptomatic COVID-19 have higher ICU admissions and prolonged length of stay (LOS) as compared with asymptomatic COVID-19 patients. The 90-day survival probability of the entire cohort was 70.1% (60.3-79.9) and was significantly lower in patients with COVID-19 symptomatic 63.4% (50.5-76.2). The cut-off preoperative values for the prediction of mortality: Ferritin ≥ 438.5 ng/mL (Area under the curve [AUC] = 0.908), C-reactive protein (CRP) ≥ 12.5 mg/dL (AUC = 0.715), leukocyte ≥ 13.8 × 103/mL (AUC = 0.706), and albumin ≤ 2.78 g/dL (AUC = 704). Furthermore, a cut-off value of CRP of ≥ 12.5 mg/dL yielded an accuracy of 82.9% for the prediction of postoperative complications (p < 0.001). CONCLUSION: Patients with symptomatic COVID-19 who needed emergency surgery have higher ICU admissions, prolonged LOS, and decreased 90-day survival as compared with asymptomatic COVID-19 patients. Preoperative ferritin, CRP, leukocytes, and albumin could be used as predictors of mortality.

ANTECEDENTES: Hay datos limitados sobre los pacientes con COVID-19 que necesitaron cirugía de emergencia. El objetivo del presente estudio fue describir los resultados perioperatorios y la mortalidad de pacientes con COVID-19 que se sometieron a cirugía de emergencia. MATERIAL Y MÉTODOS: Estudio retrospectivo de pacientes con COVID-19 sintomáticos vs. asintomáticos de marzo 2020 a febrero 2022 que requirieron cirugía de emergencia en un Hospital de Referencia Nacional. RESULTADOS: Se incluyeron 44 pacientes. Los pacientes con COVID-19 sintomático tienen más admisiones en la UCI y estancia hospitalaria prolongada en comparación con los pacientes con COVID-19 asintomático. La supervivencia a 90 días de la cohorte fue del 70,1% (60,3-79,9) y fue menor en los pacientes con COVID-19 sintomáticos del 63.4% (50.5-76.2). Los valores preoperatorios para la predicción de mortalidad: ferritina ≥ 438.5 ng/mL (AUC = 0.908), PCR ≥ 12.5 mg/dL (AUC = 0.715), leucocitos ≥ 13.8 × 103/mL (AUC = 0.706) y albúmina ≤ 2.78 g/dl (AUC = 704). La PCR de ≥ 12.5 mg/dL tiene una precisión del 82.9% para la predicción de complicaciones posoperatorias (p < 0.001). CONCLUSIÓN: Los pacientes con COVID-19 sintomático tienen más admisiones en la UCI, estancia hospitalaria prolongada y menor supervivencia en comparación con los pacientes con COVID-19 asintomáticos. La ferritina, PCR, leucocitos y albúmina preoperatoria pueden utilizarse como predictores de mortalidad.

Assessing demographic and socioeconomic factors in patients with advanced colorectal cancer.

BACKGROUND: The aim of the study was to determine the socioeconomic and demographic factors associated with advanced colorectal cancer (CRC) presentation at our institution. METHODS: From January 2009 to January 2018, patients that underwent CRC surgery at our institution were included and retrospectively analyzed. Univariate and multivariate logistic regression were used to determine independent risk factors for presenting with advanced CRC. RESULTS: A total of 277 patients were included, 53.5% presented with advanced CRC. The multivariate analysis identified that living in a rural area (odds ratio [OR] = 5.25; 95% confidence interval [95% CI]: 2.27-12-10; p < 0.001), weight loss (OR = 2.33; 95% CI: 1.35-4.09; p = 0.002), needing emergency surgery (OR = 4.68; 95% CI: 1.25-17.49; p = 0.022), location in the rectum in comparison with colon (OR = 2.66; 95% CI: 1.44-4.91; p = 0.002), and location in the mid rectum (OR = 6.10; 95% CI: 2.31-16.12; p < 0.001) were associated with higher odds of advanced CRC stage at presentation. CONCLUSIONS: Patients with lower socioeconomic status, with symptoms, and needing emergency surgery were associated with advanced CRC stage at presentation. Special interventions to improve access to care in this population should be planned to enhance CRC outcomes.

INTRODUCCIÓN: El objetivo del presente estudio es determinar los factores socioeconómicos y demográficos asociados con la presentación de cáncer colorrectal (CCR) en etapas avanzadas en nuestra institución. MÉTODOS: De Enero 2009 a Enero 2018, aquellos pacientes operados por CCR fueron incluidos y analizados de forma retrospectiva. Se realizó análisis de regresión logística para determinar los factores de riesgo independientes para presentar CCR avanzado. RESULTADOS: Se incluyeron un total de 277 pacientes, de los cuales 53.5% se diagnosticaron con CCR avanzado. En el análisis multivariable: vivienda en zona rural (OR = 5.25; 95% CI: 2.27-12-10; p < 0.001), pérdida de peso (OR = 2.33; 95% CI: 1.35-4.09; p = 0.002), necesidad de cirugía de urgencia (OR = 4.68; 95% CI: 1.25-17.49; p = 0.022), tumores en recto (OR = 2.66; 95% CI: 1.44-4.91; p = 0.002), fueron factores asociados a mayor probabilidad de presentación avanzada del CCR. CONCLUSIONES: Pacientes con nivel socioeconómico bajo, aquellos que acuden sintomáticos, y los que requieren de inicio cirugía de urgencia, fueron factores asociados a presentaciones avanzadas de CCR. Se requieren intervenciones especiales para mejorar el acceso a un diagnóstico temprano y oportuno en estos grupos poblacionales.

Two Decades of Wildlife Pathogen Surveillance: Case Study of Choclo orthohantavirus and Its Wild Reservoir Oligoryzomys costaricensis.

The Costa Rican pygmy rice rat (Oligoryzomys costaricensis) is the primary reservoir of Choclo orthohantavirus (CHOV), the causal agent of hantavirus disease, pulmonary syndrome, and fever in humans in Panama. Since the emergence of CHOV in early 2000, we have systematically sampled and archived rodents from >150 sites across Panama to establish a baseline understanding of the host and virus, producing a permanent archive of holistic specimens that we are now probing in greater detail. We summarize these collections and explore preliminary habitat/virus associations to guide future wildlife surveillance and public health efforts related to CHOV and other zoonotic pathogens. Host sequences of the mitochondrial cytochrome b gene form a single monophyletic clade in Panama, despite wide distribution across Panama. Seropositive samples were concentrated in the central region of western Panama, consistent with the ecology of this agricultural commensal and the higher incidence of CHOV in humans in that region. Hantavirus seroprevalence in the pygmy rice rat was >15% overall, with the highest prevalence in agricultural areas (21%) and the lowest prevalence in shrublands (11%). Host-pathogen distribution, transmission dynamics, genomic evolution, and habitat affinities can be derived from the preserved samples, which include frozen tissues, and now provide a foundation for expanded investigations of orthohantaviruses in Panama.

Membrane and Nuclear Absorbed Doses from 177Lu and 161Tb in Tumor Clusters: Effect of Cellular Heterogeneity and Potential Benefit of Dual Targeting-A Monte Carlo Study.

Early use of targeted radionuclide therapy to eradicate tumor cell clusters and micrometastases might offer cure. However, there is a need to select appropriate radionuclides and assess the potential impact of heterogeneous targeting. Methods: The Monte Carlo code CELLDOSE was used to assess membrane and nuclear absorbed doses from 177Lu and 161Tb (ß--emitter with additional conversion and Auger electrons) in a cluster of 19 cells (14-µm diameter, 10-µm nucleus). The radionuclide distributions considered were cell surface, intracytoplasmic, or intranuclear, with 1,436 MeV released per labeled cell. To model heterogeneous targeting, 4 of the 19 cells were unlabeled, their position being stochastically determined. We simulated situations of single targeting, as well as dual targeting, with the 2 radiopharmaceuticals aiming at different targets. Results: 161Tb delivered 2- to 6-fold higher absorbed doses to cell membranes and 2- to 3-fold higher nuclear doses than 177Lu. When all 19 cells were targeted, membrane and nuclear absorbed doses were dependent mainly on radionuclide location. With cell surface location, membrane absorbed doses were substantially higher than nuclear absorbed doses, both with 177Lu (38-41 vs. 4.7-7.2 Gy) and with 161Tb (237-244 vs. 9.8-15.1 Gy). However, when 4 cells were not targeted by the cell surface radiopharmaceutical, the membranes of these cells received on average only 9.6% of the 177Lu absorbed dose and 2.9% of the 161Tb dose, compared with a cluster with uniform cell targeting, whereas the impact on nuclear absorbed doses was moderate. With an intranuclear radionuclide location, the nuclei of unlabeled cells received only 17% of the 177Lu absorbed dose and 10.8% of the 161Tb dose, compared with situations with uniform targeting. With an intracytoplasmic location, nuclear and membrane absorbed doses to unlabeled cells were one half to one quarter those obtained with uniform targeting, both for 177Lu and for 161Tb. Dual targeting was beneficial in minimizing absorbed dose heterogeneities. Conclusion: To eradicate tumor cell clusters, 161Tb may be a better candidate than 177Lu. Heterogeneous cell targeting can lead to substantial heterogeneities in absorbed doses. Dual targeting was helpful in reducing dose heterogeneity and should be explored in preclinical and clinical studies.

Entomological Surveillance Planning Tool (ESPT)-generated actionable evidence on human and vector behaviours optimizes present interventions and reduces exposure to Anopheles vectors in two communities of Guna Yala, Panamá.

BACKGROUND: Although most of Panamá is free from malaria, localized foci of transmission persist, including in the Guna Yala region. Government-led entomological surveillance using an Entomological Surveillance Planning Tool (ESPT) sought to answer programmatically relevant questions on local entomological drivers of transmission and gaps in protection to guide local vector control decision-making. METHODS: The ESPT was used to design a sampling plan to answer priority programmatic questions about the appropriateness of Long Lasting Insecticidal Nets (LLINs) and spaces and times where humans remain exposed to Anopheles bites (gaps in protection) in the communities of Permé and Puerto Obaldía, Guna Yala. Adult Anopheles were sampled at three time points via human landing catches (HLCs) during the rainy and dry seasons (2018/2019). Human behaviour observations (HBOs) were conducted alongside HLCs to examine intervention use, indoor versus outdoor activity, and sleeping patterns. HLC and HBO data were integrated to evaluate HBO-adjusted human biting rate (HBR). RESULTS: A total of 7,431 adult Anopheles were collected across both sites. Of the 450 specimens molecularly confirmed to species-level, 75.5% (n = 340) were confirmed as Anopheles Nyssorhynchus albimanus, followed by Anopheles (Ny.) aquasalis. Anopheles host seeking activity was demonstrated to be primarily exophagic throughout all sampling periods and in both communities. When adjusted with HBOs, exposure to mosquito bites was predominantly indoors and overnight in Permé (Nov, Mar), compared to predominantly outdoors in Puerto Obaldía (Nov, Mar, Jul). Differences in site-specific human-vector exposure profiles were due to contrasting cultural and lifestyle practices between Permé and Puerto Obaldía (possibly partly influenced by the absence of electricity in Permé), and lower LLIN use in Permé. This evidence supported a previously planned LLIN campaign alongside a social behaviour change communication (SBCC) strategy in the Guna Yala Comarca (Jul 2019), which increased LLIN use. In turn, this led to a reduction of indoor exposure to mosquito bites, and a shift to predominant outdoor exposure to mosquito bites. CONCLUSION: ESPT-based question-driven planning and the integration of HBOs, intervention, and HLC data generated evidence towards answering the programmatic questions. This evidence enabled the characterization of site-specific human-vector exposure profiles, and the quantification of remaining gaps in protection. These data also provide important insights into remaining gaps in protection that must be addressed to further reduce human exposure to mosquito bites at these sites.

How to explain the sensitivity of DNA double-strand breaks yield to 125I position?

PURPOSE: Auger emitters exhibit interesting features due to their emission of a cascade of short-range Auger electrons. Maximum DNA breakage efficacy is achieved when decays occur near DNA. Studies of double-strand breaks (DSBs) yields in plasmids revealed cutoff distances from DNA axis of 10.5 Å-12 Å, beyond which the mechanism of DSBs moves from direct to indirect effects, and the yield decreases rapidly. Some authors suggested that the average energy deposited in a DNA cylinder could explain such cutoffs. We aimed to study this hypothesis in further detail. MATERIALS AND METHODS: Using the Monte Carlo code CELLDOSE, we investigated the influence of the 125I atom position on energy deposits and absorbed doses per decay not only in a DNA cylinder, but also in individual strands, each modeled as 10 spheres encompassing the fragility sites for phosphodiester bond cleavage. RESULTS: The dose per decay decreased much more rapidly for a sphere in the proximal strand than for the DNA cylinder. For example, when moving the 125I source from 10.5 Å to 11.5 Å, the average dose to the sphere dropped by 43%, compared to only 13% in the case of the cylinder. CONCLUSIONS: Explaining variations in DSBs yields with 125I position should consider the probability of inducing damage in the proximal strand (nearest to the 125I atom). The energy received by fragility sites in this strand is highly influenced by the isotropic (4π) emission of 125I low-energy Auger electrons. The positioning of Auger emitters for targeted radionuclide therapy can be envisioned accordingly.

Comparison of PvLAP5 and Pvs25 qRT-PCR assays for the detection of Plasmodium vivax gametocytes in field samples preserved at ambient temperature from remote malaria endemic regions of Panama.

BACKGROUND: As the elimination of malaria in Mesoamerica progresses, detection of Plasmodium vivax using light microscopy (LM) becomes more difficult. Highly sensitive molecular tools have been developed to help determine the hidden reservoir of malaria transmission in low transmission settings. In this study we compare the performance of PvLAP5 and Pvs25 qRT-PCR assays to LM for the detection of Plasmodium vivax gametocytes in field samples preserved at ambient temperature from malaria endemic regions of Panama. METHODS: For this purpose, we collected a total of 83 malaria field samples during 2017-2020 preserved in RNAprotect (RNAp) of which 63 (76%) were confirmed P. vivax by LM and selected for further analysis. Additionally, 16 blood samples from local healthy malaria smear negative volunteers, as well as, from 15 malaria naïve lab-bred Aotus monkeys were used as controls. To optimize the assays, we first determined the minimum blood volume sufficient for detection of PvLAP5 and Pv18SrRNA using P. vivax infected Aotus blood that was preserved in RNAp and kept either at ambient temperature for up to 8 days before freezing or was snap-frozen at -80° Celsius at the time of bleeding. We then compared the mean differences in gametocyte detection rates of both qRT-PCR assays to LM and performed a multivariate correlation analysis of study variables. Finally, we determined the sensitivity (Se) and specificity (Sp) of the assays at detecting gametocytes compared to LM. RESULTS: Blood volume optimization indicated that a blood volume of at least 60 µL was sufficient for detection of PvLAP5 and Pv18SrRNA and no significant differences were found between RNA storage conditions. Both PvLAP5 and Pvs25 qRT-PCR assays showed a 37-39% increase in gametocyte detection rate compared to LM respectively. Strong positive correlations were found between gametocytemia and parasitemia and both PvLAP5 and Pvs25 gametocyte markers. However, no significant differences were detected in the Se and Sp of the Pvs25 and PvLAP5 qRT-PCR assays, even though data from control samples suggested Pvs25 to be more abundant than PvLAP5. CONCLUSIONS: This study shows that the PvLAP5 qRT-PCR assay is as Se and Sp as the gold standard Pvs25 assay and is at least 37% more sensitive than LM at detecting P. vivax gametocytes in field samples preserved in RNAp at ambient temperature from malaria endemic regions of Panama. AUTHOR SUMMARY: Plasmodium vivax is one of the five species of malaria (P. falciparum, P. malariae, P. ovale and P. knowlesi) that are transmitted to man by the bite of female anopheles mosquitoes. It causes ~14.3 million cases mainly in Southeast Asia, India, the Western Pacific and the Americas annually. In the Americas, malaria remains a major problem in underdeveloped areas and indigenous communities in the Amazon region and eastern Panama, where it is endemic and difficult to eliminate. As malaria elimination progresses, detection of P. vivax by light microscopy (LM) becomes more difficult. Therefore, highly sensitive molecular tools have been developed that use genetic markers for the parasite to help determine the hidden reservoir of malaria transmission. This study compares the performance of two molecular assays based on the genetic markers of mature gametocytes PvLAP5 and Pvs25 with LM. The study shows that the PvLAP5 qRT-PCR assay is as sensitive and specific as the gold standard Pvs25 assay and is at least 37% more sensitive than LM at detecting P. vivax gametocytes. These data suggest that the PvLAP5 qRT-PCR assay can be a useful tool to help determine the hidden reservoir of transmission in endemic foci approaching elimination.

Surgical treatment of acute cholecystitis in patients with confirmed COVID-19: Ten case reports and review of literature.

BACKGROUND: Research concerning postoperative outcomes of confirmed coronavirus disease 2019 (COVID-19) patients revealed unfavorable postoperative results with increased morbidity, pulmonary complications and mortality. Case reports have suggested that COVID-19 is associated with more aggressive presentation of acute cholecystitis. The aim of the present study is to describe the perioperative assessment and postoperative outcomes of ten patients with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection with concomitant acute cholecystitis who underwent cholecystectomy. CASE SUMMARY: We report a total of 10 SARS-CoV-2 positive patients with concomitant acute cholecystitis that underwent cholecystectomy. Six patients were males, the mean age was 47.1 years. Nine patients had moderate acute cholecystitis, and one patient had severe acute cholecystitis. All patients were treated with urgent/early laparoscopic cholecystectomy. Regarding the Parkland grading scale, two patients received a Parkland grade of 3, two patients received a Parkland grade of 4, and six patients received a Parkland grade of 5. Eight patients required a bail-out procedure. Four patients developed biliary leakage and required endoscopic retrograde cholangiopancreatography with biliary sphincterotomy. After surgery, five patients developed acute respiratory distress syndrome (ARDS) and required intensive care unit (ICU) admission. One patient died after cholecystectomy due to ARDS complications. The mean total length of stay (LOS) was 18.2 d. The histopathology demonstrated transmural necrosis (n = 5), vessel obliteration with ischemia (n = 3), perforation (n = 3), and acute peritonitis (n = 10). CONCLUSION: COVID-19 patients with acute cholecystitis had difficult cholecystectomies, high rates of ICU admission, and a prolonged LOS.

Valoración del tratamiento del bruxismo mediante toxina botulínica / Assessment of the treatment of bruxism by botulinum toxin

El bruxismo se caracteriza por ser una actividad relacionada la activación de los músculos masticatorios de forma repetitiva y habitualmente durante el sueño. La relevancia de esta entidad reside en su asociación con erosiones y movilidad dentarias, fracturas dentales, mialgia e hipertrofia del músculo masetero y o artralgia característica. Si bien de etiología no clara se relaciona con multitud de factores fisiopatológicos. En la actualidad existen multitud de líneas de tratamiento para este problema de salud, tales como: terapia cognitivo-conductual, férulas de oclusión o de descarga, opciones farmacológicas como benzodiacepinas, y dopamina. Estas medidas habitualmente sirven como manejo de los signos y síntomas derivados del bruxismo, pero la eficacia de todas ella no es total. Actualmente, ante la necesidad de búsqueda de otras opciones terapéuticas al problema del bruxismo, múltiples ensayos han centrado su atención en la utilización de la toxina botulínica como alternativa, teniendo en cuenta su eficacia para una amplia variedad de patologías médicas y estéticas.El objetivo de esta puesta al día es actualizar el conocimiento a fecha actual de la evidencia existente acerca de la utilización de la toxina botulínica en el tratamiento del bruxismo. Para ello se seleccionan las revisiones sistemáticas existentes que incluyen los principales ensayos clínicos aleatorizados disponibles.Método: Revisión bibliográfica en las principales bases de datos utilizando las palabras “bruxismo” y/o “toxina botulínica” Resultados: Tras el análisis de las diferentes revisiones podemos decir que todos los resultados apuntan en la misma dirección: que las inyecciones de toxina botulínica en el masetero y / o los músculos temporales pueden ser una opción de tratamiento válida en pacientes con bruxismo, ya que pueden mejorar la calidad de vida.(AU)

Bruxism is characterized by being an activity related to the activation of the chewing muscles repeatedly and usually during sleep. The relevance of this entity resides in its association with tooth erosions and mobility, dental fractures, myalgia and hypertrophy of the masseter muscle and or characteristic arthralgia. Although its etiology is not clear, it is related to a multitude of pathophysiological factors. Currently there are many lines of treatment for this health problem, such as: cognitive-behavioral therapy, occlusion or discharge splints, pharmacological options such as benzodiazepines, and dopamine. These measures usually serve to manage the signs and symptoms derived from bruxism, but the effectiveness of all of them is not total. Currently, faced with the need to search for other therapeutic options for the problem of bruxism, multiple trials have focused their attention on the use of botulinum toxin as an alternative, taking into account its efficacy for a wide variety of medical and aesthetic pathologies. The objective of this update is to update the knowledge to date of the existing evidence about the use of botulinum toxin in the treatment of bruxism. For this, the existing systematic reviews that include the main available randomized clinical trials are selected. Method: Bibliographic review in the main databases using the words "bruxism" and / or "botulinum toxin" Results: After the analysis of the different reviews we can say that all the results point in the same direction: that botulinum toxin injections in the masseter and / or temporal muscles can be a valid treatment option in patients with bruxism, since they can improve the quality of life. With the exception of the systematic review by Ågren et al, 28 who do not see evidence through the tests that record electromyographic activity and bite force to recommend the use of botulinum toxin as a treatment for bruxism at the present time.(AU)

Anopheles drivers of persisting malaria transmission in Guna Yala, Panamá: an operational investigation.

BACKGROUND: Though most of Panamá is free from malaria, localized foci of transmission persist, including in the Guna Yala region. Government-led entomological surveillance using an entomological surveillance planning tool (ESPT) sought to answer programmatically-relevant questions that would enhance the understanding of both local entomological drivers of transmission and gaps in protection that result in persisting malaria transmission to guide local vector control decision-making. METHODS: The ESPT was used to design a sampling plan centered around the collection of minimum essential indicators to investigate the relevance of LLINs and IRS in the communities of Permé and Puerto Obaldía, Guna Yala, as well as to pinpoint any remaining spaces and times where humans are exposed to Anopheles bites (gaps in protection). Adult Anopheles were collected at three time points via human landing catches (HLCs), CDC Light Traps (LT), and pyrethrum spray catches (PSCs) during the rainy and dry seasons. Mosquitoes were identified to species via molecular methods. Insecticide susceptibility testing of the main vector species to fenitrothion was conducted. RESULTS: In total, 7537 adult Anopheles were collected from both sites. Of the 493 specimens molecularly confirmed to species, two thirds (n = 340) were identified as Nyssorhynchus albimanus, followed by Anopheles aquasalis. Overall Anopheles human biting rates (HBRs) were higher outdoors than indoors, and were higher in Permé than in Puerto Obaldía: nightly outdoor HBR ranged from 2.71 bites per person per night (bpn) (Puerto Obaldía), to 221.00 bpn (Permé), whereas indoor nightly HBR ranged from 0.70 bpn (Puerto Obaldía) to 81.90 bpn (Permé). Generally, peak biting occurred during the early evening. The CDC LT trap yields were significantly lower than that of HLCs and this collection method was dropped after the first collection. Pyrethrum spray catches resulted in only three indoor resting Anopheles collected. Insecticide resistance (IR) of Ny. albimanus to fenitrothion was confirmed, with only 65.5% mortality at the diagnostic time. CONCLUSION: The early evening exophagic behaviour of Anopheles vectors, the absence of indoor resting behaviours, and the presence of resistance to the primary intervention insecticide demonstrate limitations of the current malaria strategy, including indoor residual spraying (IRS) and long-lasting insecticidal nets (LLINs), and point to both gaps in protection and to the drivers of persisting malaria transmission in Guna Yala. These findings highlight the need for continued and directed entomological surveillance, based on programmatic questions, that generates entomological evidence to inform an adaptive malaria elimination strategy.

Laparoscopic appendectomy in complicated appendicitis with compromised appendix base: a retrospective cohort study.

BACKGROUND: Patients with compromised appendix base constitute a subgroup of patients with complicated appendicitis, and there is few available information. OBJECTIVE: To study the frequency of stump leaks and fistulae in patients with complicated appendicitis with compromised stump. METHOD: This is an observational, retrospective study of patients that underwent laparoscopic appendectomy with compromised appendix stump. RESULTS: From 2015 to 2019, 158 patients with complicated appendicitis were operated, of them 54 had compromised base or stump. There were 66.7% men, with a mean age of 38.7 years. For stump closure, a simple knot was employed in 57.4%, and in 42.6% an invaginated suture was employed. Regarding complications, 16.7% developed intraabdominal abscess, 7.4% ileus and 7.4% had wound infection. We found one stump leak and one stump fistula. The mean length of stay was 5.4 days (range: 1-20). There were 5 reoperations, 4 for abscess drainage and 1 for stump leak. CONCLUSIONS: Patients with acute complicated appendicitis with compromised appendicular base, laparoscopic surgery either with simple knot or with invaginated suture resulted in low frequency of stump leaks and fistula.

ANTECEDENTES: Los pacientes con base apendicular comprometida constituyen un subgrupo de pacientes con apendicitis complicada y existe poca información al respecto. OBJETIVO: Conocer la frecuencia de fístulas y fugas fecales en pacientes con apendicitis complicada con base apendicular comprometida. MÉTODO: Se trata de un estudio observacional, retrospectivo y transversal de pacientes operados de apendicectomía laparoscópica con base apendicular comprometida. RESULTADOS: De 2015 a 2019 se encontraron 158 casos de apendicitis complicada, de los cuales 54 tenían la base apendicular comprometida. Hubo predominio de varones (66.7%) y la edad media fue de 38.7 años. En el 57.4% de los casos se realizó un nudo simple y en el 42.6% un punto transfictivo con invaginación del muñón. En relación con las complicaciones, el 16.7% desarrollaron abscesos intraabdominales, el 7.4% íleo y el 7.4% infección de herida. Hubo un paciente con fuga del muñón y un paciente con fístula cecal. El tiempo medio de estancia hospitalaria fue de 5.4 días (rango: 1-20). Se realizaron cinco reintervenciones: cuatro para drenaje de absceso intraabdominal y una por fuga del muñón. CONCLUSIONES: En los pacientes con base apendicular comprometida, el manejo laparoscópico con ligadura simple o con punto transfictivo resulta en una baja frecuencia de fuga y fístula del muñón apendicular.

Uso de técnicas alternativas o de relajación como terapia al dolor crónico / Use of alternative or relaxation techniques in the treatment of chronic pain

Objetivo: Este trabajo consta de una revisión, dónde tratan el problema del dolor crónico en diferentes ámbitos y terapias alternativas o de relajación como tratamiento a este problema. Material y Método: Se han revisado los trabajos más significativos sobre las intervenciones y terapias de relajación dirigidas a reducir o eliminar el dolor en los pacientes crónicos. Se encuentran; estudios revisiones sistemática observacional, revisiones bibliográficas, estudio experimental, cuasiexperimental, estudios descriptivo transversal. Según los resultados obtenidos de la revisión sistemática realizada en el presente estudio, proceden de los países de España, Colombia, México. Resultados: Según los resultados obtenidos de la revisión sistemática realizada concluimos que las técnicas alternativas o de relajación son efectivas para la disminución del dolor crónico. Conclusiones: Se concluye que todas las intervenciones presentan algún tipo de eficacia y que la elección del tratamiento más adecuado se ha de basar en la evaluación individual de cada paciente. Así mismo se considera la necesidad de continuar la investigación y de considerar las intervenciones multidisciplinares para abordar el problema del dolor crónico. A lo largo de todo el trabajo se pone de manifiesto la utilidad del tratamiento del dolor crónico, destacando el papel que la relajación puede desempeñar a distintos niveles.(AU)

Objective: This work consists of a review, where they treat the problem of chronic pain in different settings and alternative or relaxation therapies as a treatment for this problem. Material and Method: The most significant works on relaxation interventions and therapies aimed at reducing or eliminating pain in chronic patients have been reviewed. They find each other; studies systematic observational reviews, bibliographic reviews, experimental, quasi-experimental studies, descriptive cross-sectional studies. According to the results obtained from the systematic review carried out in the present study, they come from the countries of Spain, Colombia and Mexico. Results: According to the results obtained from the systematic review carried out, we conclude that alternative or relaxation techniques are effective in reducing chronic pain. Conclusions: It is concluded that all the interventions show some type of efficacy and that the choice of the most appropriate treatment must be based on the individual evaluation of each patient. It also considers the need to continue research and consider multidisciplinary interventions to address the problem of chronic pain. Throughout the entire work, the usefulness of chronic pain treatment is highlighted, highlighting the role that relaxation can play at different levels.(AU)

Evaluación de los tratamientos del dolor crónico en artrosis / Evaluation of chronic pain treatments in arthrosis

La artrosis es una enfermedad degenerativa de las articulaciones, con una prevalencia del 10% en España, siendo la primera causa de discapacidad. El principal síntoma, y hacia el cual se dirigen la mayoría de las terapias, es el dolor. El objetivo de esta revisión bibliográfica es saber cómo se puede tratar esta enfermedad, cuales son las terapias en investigación, mostrando estudios ejemplo que nos ayuden a sacar conclusiones. Se realiza a través de la consulta de diferentes fuentes bibliográficas. Existe un tratamiento no farmacológico basado en la educación sanitaria del paciente, incluyendo prácticas como la acupuntura o los ultrasonidos, determinados alimentos, ejercicio físico y plantas medicinales. También existe un tratamiento farmacológico con analgésicos y antiinflamatorios vía oral y de acción rápida, para aliviar el dolor, como paracetamol y AINES, opioides débiles y opioides fuertes que se usan vía transdérmica en esta patología; y por último capsaicina o AINES vía tópica. Existen fármacos modificadores de la enfermedad denominados SYSADOA de acción lenta, como el condroitín sulfato, sulfato de glucosamina y diacereína. En ocasiones se hacen infiltraciones articulares con ácido hialurónico y corticoides para que actúe de forma local y sea más eficaz, e incluso a veces con toxina botulínica y otras sustancias que veremos. El tratamiento quirúrgico es otra alternativa, pero no hablaremos de ella en nuestro trabajo. El tratamiento de la artrosis se centra sobre todo en aliviar el dolor de los pacientes y mejorar su calidad de vida.(AU)

Osteoarthritis is a degenerative disease of the joints, with a prevalence of 10% in Spain, being the leading cause of disability. The main symptom, and towards which most of the therapies are directed, is pain. The objective of this bibliographic review is to know how this disease can be treated, which are the therapies under investigation, showing example studies that help us draw conclusions. It is done through the consultation of different bibliographic sources. There is a non-pharmacological treatment based on the health education of the patient, including practices such as acupuncture or ultrasounds, certain foods, physical exercise and medicinal plants. There is also a pharmacological treatment with oral and fast-acting analgesics and anti-inflammatories, to relieve pain, such as paracetamol and NSAIDs, weak opioids and strong opioids that are used transdermally in this pathology; and finally capsaicin or NSAIDs topically. There are disease-modifying drugs called SYSADOA slow-acting, such as chondroitin sulfate, glucosamine sulfate, and diacerein. Sometimes joint infiltrations are made with hyaluronic acid and corticosteroids to act locally and be more effective, and even sometimes with botulinum toxin and other substances that we will see. Surgical treatment is another alternative, but we will not talk about it in our work. Treatment of osteoarthritis is primarily focused on relieving pain for patients and improving their quality of life.(AU)

Open versus laparoscopic surgery for the treatment of diverticular colovesical fistulas: A systematic review and meta-analysis.

BACKGROUND: The aim of this study was to analyze the evidence regarding open versus laparoscopic surgery for the treatment of diverticular colovesical fistula (CVF) in terms of perioperative outcomes. METHODS: A systematic review was performed using PubMed, Cochrane, Google Scholar, and Web of Science databases for studies comparing laparoscopic versus open surgery for CVF. We pooled odds ratios (OR) and mean differences (MD) using random or fixed effects models. RESULTS: Five non-randomized studies with 227 patients met the inclusion criteria. All were retrospective studies, published between 2014 and 2020. For laparoscopic surgery, the pooled rate for conversion to laparotomy was 36%. Laparoscopic and open procedures required similar operative time (MD: -11.62; 95% confidence interval [CI]: -51.41 to 28.16). No difference was found in terms of stoma rates between laparoscopic and open surgery (OR: 1.12; 95% CI 0.44-2.86). Overall, the rate of total postoperative complications was lower in the laparoscopic group (OR: 0.55; 95% CI: 0.30-0.99). The pooled analysis showed equivalent rates of anastomotic leaks (OR: 0.61; 95% CI 0.15-2.45), surgical site infections (OR: 0.44; 95% CI 0.19-1.01), and mortality (OR: 0.18; 95% CI 0.03-1.15). The length of stay was significantly reduced with laparoscopic surgery (MD: -2.89; 95% CI -4.20 to -1.58). CONCLUSION: Among patients with CVF, the laparoscopic approach appears to have shorter hospital length of stay, with no differences in anastomotic leaks, surgical site infections, stoma rates, and mortality, when compared with open surgery.

Influencia de la Dieta Mediterránea y la actividad fásica en pacientes con Diabetes Mellitus, hipertensión Arterial e hiperlipemias en una zona de atención primaria de Albacete / Influence of the Mediterranean Diet and physical activity in patients with Diabetes Mellitus, Arterial hypertension and hyperlipemia in a primary care area of Albacete

Introducción: Es necesario combatir la inactividad física, puesto que supone el 4º riesgo de mortalidad por cualquier causa a nivel mundial, siendo el factor de riesgo más prevalente por encima de la obesidad, la diabetes o el tabaco. Objetivos: Analizar nivel de actividad física (AF) y adherencia a la dieta mediterránea en pacientes con enfermedades crónicas. Metodo. Estudio descriptivo observacional mediante la realización de encuestas a pacientes con Hipertensión arterial, diabetes Mellitus tipo 2 o Dislipemia, en edades comprendidas entre 42 y 90 años. Resultados: En nuestro estudio solo el 27.77% de los encuestados consiguen realizar el objetivo de actividad física recomendada semanalmente. El 72,2% tiene una buena adherencia a la dieta mediterránea, con una media de 9,5 puntos. Conclusiones: En nuestro estudio hay un alto grado de adherencia a Dieta Mediterranea y bajo nivel de actividad fisica.(AU)

Introduction: It is necessary to combat physical inactivity, since it represents the 4th risk of mortality from any cause worldwide, being the most prevalent risk factor above obesity, diabetes or tobacco. Objectives: To analyze the level of physical activity (PA) and adherence to the Mediterranean diet in patients with chronic diseases. Method. Observational descriptive study by conducting surveys of patients with hypertension, type 2 diabetes mellitus or dyslipidemia, aged between 42 and 90 years. Results: In our study, only 27.77% of those surveyed manage to achieve the recommended goal of physical activity weekly. 72.2% have good adherence to the Mediterranean diet, with an average of 9.5 points. Conclusions: In our study there is a high degree of adherence to the Mediterranean Diet and a low level of physical activity.(AU)

Prognostic and predictive value of neutrophil-to-lymphocyte ratio after curative rectal cancer resection: A systematic review and meta-analysis.

BACKGROUND: Neutrophil-to-lymphocyte ratio (NLR) has been shown to be associated with poor prognosis in numerous solid malignancies. Here, we quantify the prognostic value of NLR in rectal cancer patients undergoing curative-intent surgery, and compare it with platelet-to-lymphocyte ratio (PLR) and lymphocyte-to-monocyte ratio (LMR). METHODS: A comprehensive search of several electronic databases was performed through January 2021, to identify studies evaluating the prognostic impact of pretreatment NLR in patients undergoing curative rectal cancer resection. The endpoints were overall survival (OS), disease-free survival (DFS), and clinicopathologic parameters. The pooled hazard ratio (HR) or odds ratio with 95% confidence interval (CI) were calculated. RESULTS: Thirty-one studies comprising 7553 patients were assessed. All studies evaluated NLR; thirteen and six evaluated PLR and LMR, respectively. High NLR was associated with worse OS (HR 1.92, 95% CI 1.60-2.30, P < 0.001) and DFS (HR 1.83, 95% CI 1.51-2.22, P < 0.001), and the results were consistent in all subgroup analyses by treatment modality, tumor stage, study location, and NLR cut-off value, except for the subgroups limited to cohorts with cut-off value ≥ 4. The size of effect of NLR on OS and DFS was greater than that of PLR, and similar to that of LMR. Finally, high NLR was associated with lower rate of pathologic complete response. CONCLUSIONS: In the setting of curative rectal cancer resection, pretreatment NLR correlates with tumor response to neoadjuvant therapy, and along with LMR, is a robust predictor of poorer prognosis. These biomarkers may thus help risk-stratify patients for individualized treatments and enhanced surveillance.