Spatiotemporal patterns of dengue and Zika incidence during the 2015-2018 outbreak of Zika in Mexico.

OBJECTIVE: Evaluate spatially and temporally simultaneous presence of clusters of dengue and Zika clinical cases and their relationship with expected dengue transmission risk. MATERIALS AND METHODS: A classification of dengue risk transmission was carried out for whole country, and spatial autocorrelation analyses to identify clusters of confirmed clinical cases of dengue and Zika from 2015 to 2018 was conducted using Moran's Index statistics. RESULTS: Clusters of both diseases were identified in dengue-high risk munici-palities at the beginning of the outbreak, but, at the end of the outbreak, Zika clusters occurred in dengue low-risk mu-nicipalities. CONCLUSION: This study identified Zika clusters in low-risk dengue areas suggesting participation of several factors that favor virus introduction and dissemination, such as differences in entomological and control interventions, and the possibility of cross-immunity in the population.

CA19-9 capability as predictor of pancreatic cancer resectability in a Spanish cohort.

CA19-9 serum has been suggested as a marker of unresectability but different cut-off levels have been published. A cut-off of 500 U/ml is currently considered in an international consensus as biological criteria of borderline resectable pancreatic adenocarcinoma. To evaluate whether serum CA19-9 threshold of 500 U/ml could be adequate predictor of resectability in pancreatic adenocarcinoma. Multicenter, observational, prospective study performed in Spain including 203 patients diagnosed with pancreatic adenocarcinoma. 43 (21.2%) cases were resectable and 160 (78.8%) unresectable. Among the 176 preoperative CA19-9 available values, 98 (58.3%) were ≤ 500 U/ml and 73 (42.7%) > 500 U/ml. Resectability rate in those patients with CA19-9 ≤ 500 U/ml was 60% while it was found to be 18% when CA19-9 > 500 U/ml. Statistical model to predict resectability based on CA19-9 provide an AUC of 0.6618 (95% CI 0.53-0.83) when only CA19-9 values > 500 U/ml are studied. Serum levels of CA19-9 higher than 500 U/ml are indicative of unresectable disease, however reduced sensitivity and specificity lead to a limited clinical applicability for resectability.

Impaired immune reaction and increased lactate and C-reactive protein for early prediction of severe morbidity and pancreatic fistula after pancreatoduodenectomy.

BACKGROUND: Prediction of complications after pancreatoduodenectomy (PD) remains of interest. Blood parameters and biomarkers during first and second postoperative days (POD1, POD2) may be early indicators of complications. METHODS: This case-control study included 50 patients. Baseline, POD1 and POD2 values of leukocytes, neutrophils, lymphocytes, platelets, hemoglobin, C-reactive protein (CRP), procalcitonin and arterial lactate were compared between individuals presenting Clavien ≥ III morbidity, pancreatic fistula (PF) or clinically relevant PF (CRPF) and those without these morbidities. Common variables reaching significance were further analyzed in order to calculate a predictive score. RESULTS: Severe morbidity, PF and CRPF rates were 28.0%, 26.0% and 14.0%, respectively. Patients with severe morbidity had lower leukocytes on POD2 (P = 0.04). Patients with PF presented higher CRP on POD2 (P = 0.001), higher lactate on POD1 (P = 0.007) and POD2 (P = 0.008), and lower lymphocytes on POD1 (P = 0.007) and POD2 (P = 0.008). Patients with CRPF had lower leukocytes and neutrophils on POD1 (P = 0.048, P = 0.038), lower lymphocytes on POD1 (P = 0.001) and POD2 (P = 0.003), and higher CRP on POD2 (P = 0.001). Baseline parameters and procalcitonin obtained no statistical associations. Score was defined according to lymphocytes on POD1 < 650/µL and CRP on POD2 ≥ 250 mg/L allocating patients in 3 risk categories. PF and CRPF rates were statistically higher as risk category increased (P<0.001). Receiver operating characteristic curves and Hosmer-Lemeshow tests showed a good accuracy. CONCLUSIONS: Impaired immunological reaction during early postoperative period (lower leukocytes and, particularly, lymphocytes) in response to surgical aggression would favor complications after PD. Likewise, acidosis (higher arterial lactate) could behave as risk factor of PF. An elevated CRP on POD2 is also an early biomarker of PF. Our novel score based on postoperative lymphocyte count and CRP seems reliable for early prediction of PF.

A new dimensional-reducing variable obtained from original inflammatory scores is highly associated to morbidity after curative surgery for colorectal cancer.

PURPOSE: Several scores have been developed to define the inflammatory status of oncological patients. We suspect they share iterative information. Our hypothesis is that we may summarise their information into one or two new variables which will be independent. This will help us to predict, more accurately, which patients are at an increased risk of suffering postoperative complications after curative surgery for CRC. METHODS: Observational prospective study with those patients undergoing curative surgery for CRC between September 2015 and February 2017. We analysed the influence of inflammatory scores (PNI, GPS, NLR, PLR) on postoperative morbidity (overall and severe complications, anastomotic leakage and reoperation). RESULTS: Finally, 168 patients were analysed. We checked these four original scores are interrelated among them. Using a complex and innovative statistical method, we created two new independent variables (resultant A and resultant B) which resume the information coming from them. One of these two new variables (resultant A) was statistically associated to overall complications (OR, 2.239; 95% CI, 1.541-3.253; p = 0.0001), severe complications (OR, 1.773; 95% CI, 1.129-2.785; p = 0.013), anastomotic leakage (OR, 3.208; 95% CI, 1.416-7.268; p = 0.005) and reoperation (OR, 2.349; 95% CI, 1.281-4.305; p = 0.006). CONCLUSIONS: We evinced the four original scores we used share redundant information. We created two new independent new variables which resume their information. In our sample of patients, one of these variables turned out to be a great predictive factor for the four complications we analysed.

Severe morbidity after pancreatectomy is accurately predicted by preoperative pancreatic resection score (PREPARE): A prospective validation analysis from a medium-volume center.

BACKGROUND: Major morbidity in pancreatic surgery remains high. Different scores for predicting complications have been described. Preoperative pancreatic resection (PREPARE) score is based on objective preoperative variables and offers good predictive accuracy for Clavien ≥ III complications. This study aimed to validate this score and analyze other preoperative variables in a prospective study performed in a medium-volume center. METHODS: A total of 50 pancreatic resections were included. Preoperative variables were registered and PREPARE was calculated. The main outcome was severe morbidity (Clavien ≥ III) up to 30 days after discharge. The secondary outcomes were length of stay (LOS) and readmission. Statistical validation was performed to compare severe morbidity rate among the scores categories. Association with other preoperative variables (not included in PREPARE) was also tested. RESULTS: Of the 50 pancreatic resections, the severe morbidity was 34.0%, with median LOS of 11 days. Readmission rate was 25.5%. Severe morbidity rates according to PREPARE categories were 18.5% in low-risk group, 41.7% in intermediate-risk group, and 63.6% in high-risk group, respectively (P = 0.023). The accuracy was 72% (Hosmer-Lemeshow, P = 0.86). ROC curve was obtained both for PREPARE score expressed as incremental values and categorized as the three risk groups, showing an area under curve (AUC) of 0.736 (95% CI: 0.586-0.887; P = 0.007) and 0.712 (95% CI: 0.555-0.869; P = 0.015), respectively. PREPARE was significant in multivariate analysis. Median LOS was statistically higher as PREPARE category increases (9, 11 and 15 days in low-, intermediate- and high-risk groups, respectively; P = 0.009). Readmission was not associated with any variables. CONCLUSIONS: PREPARE behaves as an independent risk factor for severe morbidity after pancreatic surgery. Score validation shows good accuracy prediction. Increasing PREPARE category is also associated with longer LOS.

Intraductal papillary neoplasia of the bile duct with malignancy: a differentiated entity of cholangiocarcinoma with a better prognosis. A review of three new cases.

INTRODUCTION: Intraductal papillary neoplasms of the bile duct have been recognized as a differentiated entity to other biliary tumors since 2001. They are characterized by intraductal growth, with or without mucus production, and have malignant potential, although they have a better prognosis than other types of cholangiocarcinoma. CASE REPORTS: From January 2010 to August 2015, we included three patients with a confirmed diagnosis of bile duct intraductal papillary neoplasia with malignancy that were treated at our center. Two cases were male and one female with a mean age of 67.3 years. All three patients presented malignancy at the time of diagnosis. One patient was asymptomatic and the diagnosis was reported in the hepatectomy specimen after a liver transplant due to autoimmune hepatitis. The other two patients presented with cholestasis and acute cholangitis and the diagnosis was made based on imaging tests (computed tomography [CT] and magnetic resonance imaging [MRI]) and endoscopic retrograde cholangiopancreatography (ERCP) with brushing and a biopsy. The treatment in both cases was surgical with a left hepatectomy, and resection of the left bile duct and segment I. They did not receive adjuvant treatment. None of the cases had recurrence of the disease. DISCUSSION: Malignant intraductal papillary neoplasias of the biliary tract represent a different entity of cholangiocarcinoma with a better prognosis. Its diagnosis is based on imaging tests and histology by ERCP. The treatment is surgical, achieving a high rate of success with a low relapse rate.

[Analysis of the evidence on the efficacy and safety of CYD-TDV dengue vaccine and its potential licensing and implementation through Mexico's Universal Vaccination Program]. / Análisis de la evidencia sobre eficacia y seguridad de la vacuna de dengue CYD-TDV y su potencial registro e implementación en el Programa de Vacunación Universal de México.

Dengue is a major global public health problem affecting Latin America and Mexico Prevention and control measures, focusing on epidemiological surveillance and vector control, have been partially effective and costly, thus, the development of a vaccine against dengue has created great expectations among health authorities and scientific communities worldwide. The CYD-TDV dengue vaccine produced by Sanofi-Pasteur is the only dengue vaccine evaluated in phase 3 controlled clinical trials. Notwithstanding the significant contribution to the development of a vaccine against dengue, the three phase 3 clinical studies of CYD-TDV and the meta-analysis of the long-term follow up of those studies, have provided evidence that this vaccine exhibited partial vaccine efficacy to protect against virologically confirmed dengue and lead to four considerations: a) adequate vaccine efficacy against dengue virus (DENV) infections 3 and 4, less vaccine efficacy against DENV 1 and no protection against infection by DENV 2; b) decreased vaccine efficacy in dengue seronegative individuals at the beginning of the vaccination; c) 83% and 90% protection against hospitalizations and severe forms of dengue, respectively, at 25 months follow-up; and d) increased hospitalization for dengue in the vaccinated group, in children under nine years of age at the time of vaccination, detected since the third year of follow-up. The benefit of the CYD-TDV vaccine can be summarized in the protection against infection by DENV 3 and 4, as well as protection for hospitalizations and severe cases in people over nine years, who have had previous dengue infection, working mainly as a booster. In this review we identified elements on efficacy and safety of this vaccine that must be taken into account in the licensing process and potential inclusion in the national vaccination program of Mexico. The available scientific evidence on the CYD-TDV vaccine shows merits, but also leads to relevant questions that should be answered to properly assess the safety profile of the product and the target populations of potential benefit. In this regard we consider it would be informative to complete the 6-year follow-up after starting vaccination, according to the company's own study protocol recommended by the World Health Organization. As with any new vaccine, the potential licensing and implementation of the CYD-TDV as part of Mexico's vaccination program, requires a clear definition of the balance between the expected benefits and risks. Particularly with a vaccine with variable efficacy and some signs of risk, in the probable case of licensing, the post-licensed period must involve the development of detailed protocols to immediately identify risks or any health event associated with vaccination.

Graft versus host disease as a complication after liver transplantation: A rare but serious association.

UNLABELLED: The graft versus host disease after liver transplant is rare, with an incidence less than 1%, but with a high mortality (75-85%), especially due to infectious complications. It usually affects gastrointestinal tract, skin and blood system in the context of a normal liver graft function. There is no consensus on the most appropriate treatment: some articles support a reduction or even elimination of immunosuppressive drugs, while others published success with a dose increase. CLINICAL CASE: We report a case of a 68 year-old liver transplant recipient with a graft retrieved from an ABO identical cadaveric donor. After an uneventful postoperative period, he was readmitted presenting these symptoms: skin lesions, diarrhea and kidney failure. After ruling out infectious causes or drug toxicity, skin, duodenum and colon biopsies demonstrated characteristic histological changes of graft versus host disease grade III. Initially, supportive treatment along with methylprednisolone bolus were administered with good response. However, as the doses of corticosteroids decreased, the patient worsened again, requiring basiliximab. In spite of that, the patient progressively worsened with hematological involvement and, finally, an alteration of liver function tests prior to decease. The autopsy showed CMV and Herpes virus superinfection. DISCUSSION: We report a new case of graft-versus-host disease after liver transplantation with fatal evolution due to viral superinfection despite the employed measures.

Duodenal involvement by seminomatous tumors.

Testicular germ cell tumors, though rare (1%), represent the most common neoplasm among young men. Gastrointestinal involvement from these malignancies usually presents as bowel obstruction and digestive bleeding, but their frequency is low (5%). The patterns of this involvement are: infiltration from affected retroperitoneal lymph nodes or, less frequently, by peritoneal seeding and direct hematogenous spread. Particularly, infiltration of duodenum is also rare, though its real frequency is not well defined. Moreover, the affinity for GI tract differs among the histological types of GCT, being seminomatous tumors an exceedingly unfrequent cause of duodenal infiltration. We herein present a recent case in our institution of severe anemia due to gastrointestinal bleeding in the context of giant retroperitoneal bulky metastatic mass infiltrating duodenum as first manifestation of a testicular pure seminoma.

Repeated pancreatic resection for pancreatic metastases from renal cell Carcinoma: A Spanish multicenter study (PANMEKID).

BACKGROUND AND OBJECTIVES: Recurrent isolated pancreatic metastasis from Renal Cell Carcinoma (RCC) after pancreatic resection is rare. The purpose of our study is to describe a series of cases of relapse of pancreatic metastasis from renal cancer in the pancreatic remnant and its surgical treatment with a repeated pancreatic resection, and to analyse the results of both overall and disease-free survival. METHODS: Multicenter retrospective study of patients undergoing pancreatic resection for RCC pancreatic metastases, from January 2010 to May 2020. Patients were grouped into two groups depending on whether they received a single pancreatic resection (SPS) or iterative pancreatic resection. Data on short and long-term outcome after pancreatic resection were collected. RESULTS: The study included 131 pancreatic resections performed in 116 patients. Thus, iterative pancreatic surgery (IPS) was performed in 15 patients. The mean length of time between the first pancreatic surgery and the second was 48.9 months (95 % CI: 22.2-56.9). There were no differences in the rate of postoperative complications. The DFS rates at 1, 3 and 5 years were 86 %, 78 % and 78 % vs 75 %, 50 % and 37 % in the IPS and SPS group respectively (p = 0.179). OS rates at 1, 3, 5 and 7 years were 100 %, 100 %, 100 % and 75 % in the IPS group vs 95 %, 85 %, 80 % and 68 % in the SPS group (p = 0.895). CONCLUSION: Repeated pancreatic resection in case of relapse of pancreatic metastasis of RCC in the pancreatic remnant is justified, since it achieves OS results similar to those obtained after the first resection.

Clipping for endoscopic perforations: initial success but late complication requiring surgery.

INTRODUCTION: This response discusses the article by Kim and colleagues entitled "endoscopic clip closure versus surgery for the treatment of iatrogenic colon perforations developed during diagnostic colonoscopy: a review of 115,285 patients". Iatrogenic colonoscopic perforation, although uncommon, implies serious management problems for endoscopists and surgeons. Nonoperative treatment currently is recommended under certain conditions, and endoscopic clips can primarily close iatrogenic perforations, helping to avoid surgery. Of the 27 colonoscopic perforation cases presented in the article by Kim and colleagues, 16 were managed by endoscopic clipping closure and 11 by primary surgery. Conservative treatment failed for three patients. Only perforation size obtained statistical significance among the nine variables contrasted between the 11 cases with primary surgery and the 13 cases with successful endoscopic clipping. The results for the three patients whose endoscopic closure failed are not reported. AUTHORS' OPINION: The authors of this letter think it would have been interesting if these three patients had been included in the analysis due to the high importance of discovering factors that can predict failure of endoscopic clipping for perforations. CONCLUSIONS: To call attention to possible late complications requiring surgery even when initial conservative management of endoscopic perforation succeeds, the authors of this letter present a case of a colocutaneous (actually, sigmoid-scrotal) fistula in a patient 2 weeks after an apparently successful closure of colonoscopic perforation with an "over-the-scope" clip.

Transcriptome of the adult female malaria mosquito vector Anopheles albimanus.

BACKGROUND: Human Malaria is transmitted by mosquitoes of the genus Anopheles. Transmission is a complex phenomenon involving biological and environmental factors of humans, parasites and mosquitoes. Among more than 500 anopheline species, only a few species from different branches of the mosquito evolutionary tree transmit malaria, suggesting that their vectorial capacity has evolved independently. Anopheles albimanus (subgenus Nyssorhynchus) is an important malaria vector in the Americas. The divergence time between Anopheles gambiae, the main malaria vector in Africa, and the Neotropical vectors has been estimated to be 100 My. To better understand the biological basis of malaria transmission and to develop novel and effective means of vector control, there is a need to explore the mosquito biology beyond the An. gambiae complex. RESULTS: We sequenced the transcriptome of the An. albimanus adult female. By combining Sanger, 454 and Illumina sequences from cDNA libraries derived from the midgut, cuticular fat body, dorsal vessel, salivary gland and whole body, we generated a single, high-quality assembly containing 16,669 transcripts, 92% of which mapped to the An. darlingi genome and covered 90% of the core eukaryotic genome. Bidirectional comparisons between the An. gambiae, An. darlingi and An. albimanus predicted proteomes allowed the identification of 3,772 putative orthologs. More than half of the transcripts had a match to proteins in other insect vectors and had an InterPro annotation. We identified several protein families that may be relevant to the study of Plasmodium-mosquito interaction. An open source transcript annotation browser called GDAV (Genome-Delinked Annotation Viewer) was developed to facilitate public access to the data generated by this and future transcriptome projects. CONCLUSIONS: We have explored the adult female transcriptome of one important New World malaria vector, An. albimanus. We identified protein-coding transcripts involved in biological processes that may be relevant to the Plasmodium lifecycle and can serve as the starting point for searching targets for novel control strategies. Our data increase the available genomic information regarding An. albimanus several hundred-fold, and will facilitate molecular research in medical entomology, evolutionary biology, genomics and proteomics of anopheline mosquito vectors. The data reported in this manuscript is accessible to the community via the VectorBase website (http://www.vectorbase.org/Other/AdditionalOrganisms/).

Pancreatic metastases from renal cell carcinoma. Postoperative outcome after surgical treatment in a Spanish multicenter study (PANMEKID).

BACKGROUND: Renal Cell Carcinoma (RCC) occasionally spreads to the pancreas. The purpose of our study is to evaluate the short and long-term results of a multicenter series in order to determine the effect of surgical treatment on the prognosis of these patients. METHODS: Multicenter retrospective study of patients undergoing surgery for RCC pancreatic metastases, from January 2010 to May 2020. Variables related to the primary tumor, demographics, clinical characteristics of metastasis, location in the pancreas, type of pancreatic resection performed and data on short and long-term evolution after pancreatic resection were collected. RESULTS: The study included 116 patients. The mean time between nephrectomy and pancreatic metastases' resection was 87.35 months (ICR: 1.51-332.55). Distal pancreatectomy was the most performed technique employed (50 %). Postoperative morbidity was observed in 60.9 % of cases (Clavien-Dindo greater than IIIa in 14 %). The median follow-up time was 43 months (13-78). Overall survival (OS) rates at 1, 3, and 5 years were 96 %, 88 %, and 83 %, respectively. The disease-free survival (DFS) rate at 1, 3, and 5 years was 73 %, 49 %, and 35 %, respectively. Significant prognostic factors of relapse were a disease free interval of less than 10 years (2.05 [1.13-3.72], p 0.02) and a history of previous extrapancreatic metastasis (2.44 [1.22-4.86], p 0.01). CONCLUSIONS: Pancreatic resection if metastatic RCC is found in the pancreas is warranted to achieve higher overall survival and disease-free survival, even if extrapancreatic metastases were previously removed. The existence of intrapancreatic multifocal compromise does not always warrant the performance of a total pancreatectomy in order to improve survival.

[Automated geospatial model for health services strategic planning]. / Modelo geoespacial automatizado para la regionalización operativa en planeación de redes de servicios de salud.

OBJECTIVE: To develop an automated model for the operational regionalization needed in the planning of the health service networks proposed by the new Mexican health care model (Modelo Integrador de Servicios de Salud MIDAS). MATERIAL AND METHODS: Using available data for México during 2005 and 2007, a geospatial model was developed to estimate potential catchment areas around health facilities based on access travel time. The results were compared with an operational regionalization (ERO) study manually carried out in Oaxaca with 2005 data. RESULTS: The ERO assigned 48% of villages to health care centers further away than those assigned by the geospatial model, and 23% of these health centers referred patients to more distant hospitals. CONCLUSIONS: The model calculated by this study generated a more efficient regionalization than the ERO model, minimizing travel time to access health services. This model has been adopted by the General Department of Health Planning and Development of the Mexican Ministry of Health for the implementation of the Health Sector Infrastructure Master Plan.

Prognostic Nutritional Index predicts morbidity after curative surgery for colorectal cancer. / El Prognostic Nutritional Index predice la morbilidad postoperatoria tras la cirugía curativa del cáncer colorrectal.

INTRODUCTION: Colorectal cancer (CRC) is a major health concern and it is associated with significant morbidity and mortality. Over the last decades, the relationship between cancer and nutritional and inflammatory status in oncologic patients was studied thoroughly and multiple immunonutritional scores were developed. These scores have been mainly related to the prognosis of several cancers. An interaction between the tumour and the host is generated, triggering a systemic inflammatory reaction leading to several neuroendocrine changes. This situation favours a tendency towards anorexia and catabolism. Our hypothesis is that nutritional and inflammatory status of oncologic patients is correlated to postoperative morbidity. METHODS: This is a prospective observational cohort study with those patients undergoing curative surgery for CRC at our institution between September 2015 and March 2017. Nutritional and inflammatory status was established using Onodera's Prognostic Nutritional Index (PNI). Complications (overall, severe, infectious and anastomotic leakage) were carefully collected during the first 30 days of the postoperative period. RESULTS: After carrying out the multivariate analysis, PNI turned out to be a great predictive and protective factor for overall complications (RR: 0.279; 95% CI: 0.141-0.552), severe complications (RR: 0.355; 95% CI: 0.130-0.965), infectious complications (RR: 0.220; 95% CI: 0.099-0.489) and anastomotic leakage (RR: 0.151; 95% CI: 0.036-0.640). CONCLUSION: Our work reports that PNI is an independent predictive factor for the development of postoperative complications following curative surgery for CRC.