Assessment of postoperative morbidity in Spanish hospitals: Results from a national survey.

BACKGROUND: The methodology used for recording, evaluating and reporting postoperative complications (PC) is unknown. The aim of the present study was to determine how PC are recorded, evaluated, and reported in General and Digestive Surgery Services (GDSS) in Spain, and to assess their stance on morbidity audits. METHODS: Using a cross-sectional study design, an anonymous survey of 50 questions was sent to all the heads of GDSS at hospitals in Spain. RESULTS: The survey was answered by 67 out of 222 services (30.2%). These services have a reference population (RP) of 15 715 174 inhabitants, representing 33% of the Spanish population. Only 15 services reported being requested to supply data on morbidity by their hospital administrators. Eighteen GDSS, with a RP of 3 241 000 (20.6%) did not record PC. Among these, 7 were accredited for some area of training. Thirty-six GDSS (RP 8 753 174 (55.7%) did not provide details on all PC in patients' discharge reports. Twenty-four (37%) of the 65 GDSS that had started using a new surgical procedure/technique had not recorded PC in any way. Sixty-five GDSS were not concerned by the prospect of their results being audited, and 65 thought that a more comprehensive knowledge of PC would help them improve their results. Out of the 37 GDSS that reported publishing their results, 27 had consulted only one source of information: medical progress records in 11 cases, and discharge reports in 9. CONCLUSIONS: This study reflects serious deficiencies in the recording, evaluation and reporting of PC by GDSS in Spain.

Experimental structure based drug design (SBDD) applications for anti-leishmanial drugs: A paradigm shift?

Leishmaniasis is a group of neglected tropical diseases caused by at least 20 species of Leishmania protozoa, which are spread by the bite of infected sandflies. There are three main forms of the disease: cutaneous leishmaniasis (CL, the most common), visceral leishmaniasis (VL, also known as kala-azar, the most serious), and mucocutaneous leishmaniasis. One billion people live in areas endemic to leishmaniasis, with an annual estimation of 30,000 new cases of VL and more than 1 million of CL. New treatments for leishmaniasis are an urgent need, as the existing ones are inefficient, toxic, and/or expensive. We have revised the experimental structure-based drug design (SBDD) efforts applied to the discovery of new drugs against leishmaniasis. We have grouped the explored targets according to the metabolic pathways they belong to, and the key achieved advances are highlighted and evaluated. In most cases, SBDD studies follow high-throughput screening campaigns and are secondary to pharmacokinetic optimization, due to the majoritarian belief that there are few validated targets for SBDD in leishmaniasis. However, some SBDD strategies have significantly contributed to new drug candidates against leishmaniasis and a bigger number holds promise for future development.

Second annual report from the ISSPP PIPAC database.

Objectives: To monitor the results of PIPAC directed therapy based on data from the International Society for the Study of the Pleura and Peritoneum (ISSPP) PIPAC database. Methods: Analysis of data from patients entered between June 15th, 2020, and February 28th, 2023. Results: Twelve centers reported 2,456 PIPAC procedures in 809 patients (median 2, range 1-18) with peritoneal metastasis (PM) from different primary tumors. Approximately 90 % had systemic chemotherapy prior to PIPAC. Twenty-eight percent were treated in prospective protocols. Overall non-access rate was 3.5 %. Concomitant surgical procedures were performed during PIPAC in 1.6 % of the patients. Median length of stay was 2 days. A total of 95 surgical complications were recorded, but only 22 % of these were graded ≥3b. Seventeen-hundred-and-three adverse events were noted, and 8 % were classified ≥3. The rate of complete or major histological response (peritoneal regression grade score, PRGS≤2) increased between the first and the third PIPAC in the group of patients who were evaluated by PRGS, and a PRGS ≤2 or a reduction of the mean PRGS of at least 1 between first and third PIPAC were observed in 80 %. Disease progression (50 %) or technical issues (19 %) were the most important reasons for stopping PIPAC treatment. Median overall survival from first PIPAC directed treatment varied from 10.7 months (CI 8.7-12.5) in gastric cancer to 27.1 months (16.4-50.5) in mesothelioma. Conclusions: The ISSPP PIPAC database provides substantial real-world data supporting the use of PIPAC directed therapy in patients with PM from different primary tumors.

Motor Activity-Induced White Matter Repair in White Matter Stroke.

Subcortical white matter stroke (WMS) is a progressive disorder which is demarcated by the formation of small ischemic lesions along white matter tracts in the CNS. As lesions accumulate, patients begin to experience severe motor and cognitive decline. Despite its high rate of incidence in the human population, our understanding of the cause and outcome of WMS is extremely limited. As such, viable therapies for WMS remain to be seen. This study characterizes myelin recovery following stroke and motor learning-based rehabilitation in a mouse model of subcortical WMS. Following WMS, a transient increase in differentiating oligodendrocytes occurs within the peri-infarct in young male adult mice, which is completely abolished in male aged mice. Compound action potential recording demonstrates a decrease in conduction velocity of myelinated axons at the peri-infarct. Animals were then tested on one of three distinct motor learning-based rehabilitation strategies (skilled reach, restricted access to a complex running wheel, and unrestricted access to a complex running wheel) for their capacity to induce repair. These studies determined that unrestricted access to a complex running wheel alone increases the density of differentiating oligodendrocytes in infarcted white matter in young adult male mice, which is abolished in aged male mice. Unrestricted access to a complex running wheel was also able to enhance conduction velocity of myelinated axons at the peri-infarct to a speed comparable to naive controls suggesting functional recovery. However, there was no evidence of motor rehabilitation-induced remyelination or myelin protection.SIGNIFICANCE STATEMENT White matter stroke is a common disease with no medical therapy. A form of motor rehabilitation improves some aspects of white matter repair and recovery.

Selective loss of CD107a TIGIT+ memory HIV-1-specific CD8+ T cells in PLWH over a decade of ART.

The co-expression of inhibitory receptors (IRs) is a hallmark of CD8+ T-cell exhaustion (Tex) in people living with HIV-1 (PLWH). Understanding alterations of IRs expression in PLWH on long-term antiretroviral treatment (ART) remains elusive but is critical to overcoming CD8+ Tex and designing novel HIV-1 cure immunotherapies. To address this, we combine high-dimensional supervised and unsupervised analysis of IRs concomitant with functional markers across the CD8+ T-cell landscape on 24 PLWH over a decade on ART. We define irreversible alterations of IRs co-expression patterns in CD8+ T cells not mitigated by ART and identify negative associations between the frequency of TIGIT+ and TIGIT+ TIM-3+ and CD4+ T-cell levels. Moreover, changes in total, SEB-activated, and HIV-1-specific CD8+ T cells delineate a complex reshaping of memory and effector-like cellular clusters on ART. Indeed, we identify a selective reduction of HIV-1 specific-CD8+ T-cell memory-like clusters sharing TIGIT expression and low CD107a that can be recovered by mAb TIGIT blockade independently of IFNγ and IL-2. Collectively, these data characterize with unprecedented detail the patterns of IRs expression and functions across the CD8+ T-cell landscape and indicate the potential of TIGIT as a target for Tex precision immunotherapies in PLWH at all ART stages.

Traumatismo esplénico secundario a colonoscopia: una complicación infrecuente

Introducción: La colonoscopia es un procedimiento frecuente y seguro, no exento sin embargo de complicaciones. El traumatismo esplénico es una complicación infrecuente, pero potencialmente mortal. Caso Clínico: Mujer de 75 años, consultaba por dolor y distensión abdominal tras colonoscopia. A la exploración presentaba dolor a la palpación en epigastrio e hipocondrio izquierdo sin irritación peritoneal. La TC urgente informaba de hematoma esplénico de 10 x 2,6 cm sin signos de sangrado activo. Fue tratada de forma conservadora con evolución favorable. Conclusión: El manejo del traumatismo esplénico depende de la estabilidad hemodinámica, el grado de la lesión y la presencia de sangrado activo. En casos seleccionados, el tratamiento conservador constituye una alternativa para evitar cirugías innecesarias, aunque se debe monitorizar al paciente de forma estricta durante 48-72 h en una Unidad de Cuidados Intensivo. Aunque la lesión esplénica secundaria a la colonoscopia es una complicación infrecuente, puede presentar alta morbimortalidad si pasa inadvertida.

Introduction: Colonoscopy is a frequent and routine procedure, and even though it is considered safe, it can have complications. The splenic traumatism is an infrequent complication, but potentially mortal. Clinical Case: Woman 75 years old, consulted for abdominal pain and distension after a colonoscopy. Physical examination revealed pain in epigastric and left hypochondrium without peritoneal irritation. Urgent TC scan reported a splenic hematoma of 10 x 2,6 cm, without active bleeding. She received non-operative treatment with a favorable evolution. Conclusion: The management depends on the hemodynamic stability, the grade of injury and the presence of and active bleeding. In selected cases, non-operative treatment is an option that avoids unnecessary surgeries, even if the patient must stay 48-72 h hospitalized in an Intensive Care Unit for a strict monitoring of vital signs. Although the splenic injury secondary a colonoscopy is an infrequent complication, it can be potentially mortal if it is not diagnosed.

Subcortical White Matter Stroke in the Mouse: Inducing Injury and Tracking Cellular Proliferation.

Here, we describe a method for inducing subcortical white matter stroke in mice, as well as tracking cellular proliferation through drinking water administration of EdU and ex vivo labeling.

GIST is not all that it seems.

We present a 41-year-old female who was admitted to our hospital with a history of 2-month epigastric pain and vomiting. Physical examination was normal. Upper gastrointestinal endoscopy showed a sessile submucosal tumor with central ulceration in the gastric body-antrum. Biopsies revealed a gastric mucosa without changes. Nevertheless, endoscopic ultrasound-guided biopsies showed interlacing bundles of spindle cells. The immunohistochemical study was negative for CD117 and smooth muscle actin and positive for S100 protein. A CT scan identified a heterogeneous mass in the stomach wall.

Monitoring of Circulating Tumor DNA Predicts Response to Treatment and Early Progression in Follicular Lymphoma: Results of a Prospective Pilot Study.

PURPOSE: Follicular lymphoma (FL) is the most frequent indolent non-Hodgkin lymphoma. Around 20% of patients suffer early disease progression within 24 months (POD24) of diagnosis. This study examined the significance of circulating tumor DNA (ctDNA) in predicting response to therapy and POD24 in patients with FL. EXPERIMENTAL DESIGN: We collected 100 plasma samples, before and during the treatment, from 36 patients with FL prospectively enrolled in 8 Spanish hospitals. They were treated with a chemotherapy-rituximab regimen and followed up for a median of 3.43 years. We performed targeted deep sequencing in cell-free DNA (cfDNA) and tumor genomic DNA from 31 diagnostic biopsy samples. RESULTS: Of the alterations detected in the diagnostic tissue samples, 73% (300/411) were also identified in basal cfDNA. The mean numbers of alterations per basal cfDNA sample in patients who suffered progression of disease within 24 months (POD24-pos) or did not achieve complete response (non-CR) were significantly higher than in POD24-neg or CR patients (unpaired samples t test, P = 0.0001 and 0.001, respectively). Pretreatment ctDNA levels, as haploid genome equivalents per milliliter of plasma, were higher in patients without CR (P = 0.02) and in POD24-pos patients compared with POD24-neg patients (P < 0.001). Dynamic analysis showed that ctDNA levels decreased dramatically after treatment, although the reduction was more significant in patients with CR and POD24-neg patients. CONCLUSIONS: Basal ctDNA levels are associated with the risk of early progression and response to treatment in FL. cfDNA monitoring and genotyping during treatment and follow-up predict response to treatment and early progression.

Different Brain Phenotypes in Magnetic Resonance Imaging of Healthy Children after Prenatal Insults.

In this study, we used magnetic resonance imaging (MRI) to identify the different brain phenotypes within apparently healthy children and to evaluate whether these phenotypes had different prenatal characteristics. We included 65 healthy children (mean age, 10 years old) with normal neurological examinations and without structural abnormalities. We performed cluster analyses to identify the different brain phenotypes in the brain MRI images. We performed descriptive analyses, including demographic and perinatal characteristics, to assess the differences between the clusters. We identified two clusters: Cluster 1, or the "small brain phenotype" (n = 44), which was characterized by a global reduction in the brain volumes, with smaller total intracranial volumes (1044.53 ± 68.37 vs. 1200.87 ± 65.92 cm3 (p < 0.001)), total grey-matter volumes (644.65 ± 38.85 vs. 746.79 ± 39.37 cm3 (p < 0.001)), and total white-matter volumes (383.68 ± 40.17 vs. 443.55 ± 36.27 cm3 (p < 0.001)), compared with Cluster 2, or the "normal brain phenotype" (n = 21). Moreover, almost all the brain areas had decreased volumes, except for the ventricles, caudate nuclei, and pallidum areas. The risk of belonging to "the small phenotype" was 82% if the child was preterm, 76% if he/she was born small for his/her gestational age and up to 80% if the mother smoked during the pregnancy. However, preterm birth appears to be the only substantially significant risk factor associated with decreased brain volumes.

Total en bloc spondylectomy for the L5 metastasis of a carcinoid tumor: illustrative case.

BACKGROUND: Total en bloc spondylectomy (TES) was designed to achieve oncological complete tumor resection in a vertebral compartment. Because of the special anatomy of the lumbosacral junction, TES procedure at the L5 level is a challenge, and it has been explained in few reports in the literature. Performing TES in the lower lumbar region, as normal, is accomplished by using a combined approach. OBSERVATIONS: The authors presented the case of a 20-year-old man with an isolated spinal metastasis at the L5 level of carcinoid tumor of jejunum, limited to the vertebral body. Due to good long-term prognosis, after multidisciplinary evaluation the authors decided to treat the patient with TES through a combined posteroanterior approach, with posterior instrumentation and anterior reconstruction. Nine years after surgery, the patient was asymptomatic, with no sign of local recurrence. LESSONS: TES is a feasible technique to provide long-term survival in a select subgroup of patients, reducing the risk of local recurrence. The authors presented some anatomical and biomechanical factors that must be considered at the lumbosacral region. Despite the high rates of complication associated with TES, most patients benefit from local control provided by the technique.

Development and validation of a questionnaire to evaluate satisfaction of the patient with diabetes at the primary care level.

Aims: To develop and validate a new instrument to measure satisfaction with integral care (doctor-nurse) of the patient with type 2 diabetes mellitus, considering expectations-experiences together for the primary level of care. Methods: The instrument was constructed with questions regarding integral care to measure the satisfaction of the diabetes patient and was classified into four domains. The validity of the content was done through a panel of experts, apparent validity through a focus group, the validity of the construct through analysis of the main components and confirmatory factorial analysis, instrument reliability with internal consistency, determined by Cronbach alpha and temporal stability (test-retest). Results: The reliability of the questionnaire was 0.942. The intraclass correlation coefficient was 0.849. Validity of the construct showed acceptable goodness-of-fit and factorial structure with four factors: communication, empathy, technical care, care continuity, and 24 items for each domain, giving a Kayser-Meyer-Olkin index above 0.80 and a total variance above 73. Conclusions: The instrument is reliable and is also valid in terms of up into construct and content to evaluate satisfaction. Practice Implications: In addition, these results allow to have elements for the design of strategies aimed at improving the relationship of health personnel with the patient.

Lumen-apposing metal stent deployment failure.

Endoscopic ultrasound-guided transmural drainage has become a first-line therapy for pancreatic fluid collections (1). The appearance of lumen-apposing metal stents has resulted in an authentic revolution, due to their efficacy (clinical success rate of 93%) and easy deployment (technical success rate of 98%) (2). They are associated with a shorter procedure time, lower risk of migration and a wider lumen, which could provide a more effective drainage (3). We report the case of a 78-year-old male who developed an infected pancreatic pseudocyst as a late complication of an acalculous severe acute pancreatitis. An endoscopic ultrasound-guided transmural drainage was performed after a failed computed tomography-guided percutaneous drainage with placement of a pig-tail catheter. A gastrocystic fistula was created and an AxiosTM lumen-apposing metal stent (Boston Scientific; Massachusetts, United States) was inserted. Nevertheless, it remained lodged in the pancreatic pseudocyst at the time of deployment. A computed tomography scan confirmed stent placement inside the collection (Figure 1). After endoscopic balloon dilatation of gastrocystic fistulous tract, removal was unsuccessful with proximal traction of the lumen stent flange using biopsy forceps. Surgical treatment was decided and a gastrotomy was performed, the fistula was identified in the posterior gastric wall and the stent was removed. Endoscopic ultrasound-guided transmural drainage of pancreatic fluid collections using lumen-apposing metal stents is a safe procedure. However, it is not exempt of complications such as stent migration, bleeding, gastrointestinal perforation and air embolism (4). Technical failure of lumen-apposing metal stents deployment is a rare complication that may require surgical treatment if endoscopic removal is not possible.

Correlation of RECIST, Computed Tomography Morphological Response, and Pathological Regression in Hepatic Metastasis Secondary to Colorectal Cancer: The AVAMET Study.

Background: The prospective phase IV AVAMET study was undertaken to correlate response evaluation criteria in solid tumors (RECIST)-defined response rates with computed tomography-based morphological criteria (CTMC) and pathological response after liver resection of colorectal cancer metastases. Methods: Eligible patients were aged ≥18 years, with Eastern Cooperative Oncology Group (ECOG) performance status 0/1 and histologically-confirmed colon or rectal adenocarcinoma with measurable liver metastases. Preoperative treatment was bevacizumab (7.5 mg on day 1) + XELOX (oxaliplatin 130 mg/m2, capecitabine 1000 mg/m2 bid on days 1-14 q3w). After three cycles, response was evaluated by a multidisciplinary team. Patients who were progression-free and metastasectomy candidates received one cycle of XELOX before undergoing surgery 3-5 weeks later, followed by four cycles of bevacizumab + XELOX. Results: A total of 83 patients entered the study; 68 were eligible for RECIST, 67 for CTMC, and 51 for pathological response evaluation. Of these patients, 49% had a complete or partial RECIST response, 91% had an optimal or incomplete CTMC response, and 81% had a complete or major pathological response. CTMC response predicted 37 of 41 pathological responses versus 23 of 41 responses predicted using RECIST (p = 0.008). Kappa coefficients indicated a lack of correlation between the results of RECIST and morphological responses and between morphological and pathological response rates. Conclusion: CTMC may represent a better marker of pathological response to bevacizumab + XELOX than RECIST in patients with potentially-resectable CRC liver metastases.