Subtotal laparoscopic cholecystectomy versus conversion to open as a bailout procedure: a cohort study.

BACKGROUND: The aim of this study is to evaluate morbidity and mortality in patients taken to conversion to open procedure (CO) and subtotal laparoscopic cholecystectomy (SLC) as bailout procedures when performing difficult laparoscopic cholecystectomy. METHOD: This observational cohort study retrospectively analyzed patients taken to SLC or CO as bailout surgery during difficult laparoscopic cholecystectomy between 2014 and 2022. Univariable and multivariable logistic regression models were used to identify prognostic factors for morbimortality. RESULTS: A total of 675 patients were included. Of the 675 patients (mean [SD] age 63.85 ± 16.00 years; 390 [57.7%] male) included in the analysis, 452 (67%) underwent CO and 223 (33%) underwent SLC. Overall, neither procedure had an increased risk of major complications (89 [19.69%] vs 35 [15.69%] P.207). However, CO had an increased risk of bile duct injury (18 [3.98] vs 1 [0.44] P.009), bleeding (mean [SD] 165.43 ± 368.57 vs 43.25 ± 123.42 P < .001), intestinal injury (20 [4.42%] vs 0 [0.00] P.001), and wound infection (18 [3.98%] vs 2 [0.89%] P.026), while SLC had a higher risk of bile leak (15 [3.31] vs 16 [7.17] P.024). On the multivariable analysis, Charlson comorbidity index (odds ratio [OR], 1.20; CI95%, 1.01-1.42), use of anticoagulant agents (OR, 2.56; CI95%, 1.21-5.44), classification of severity of cholecystitis grade III (OR, 2.96; CI95%, 1.48-5.94), and emergency admission (OR, 6.07; CI95%, 1.33-27.74) were associated with presenting major complications. CONCLUSIONS: SLC was less associated with complications; however, there is scant evidence on its long-term outcomes. Further research is needed on SLC to establish if it is the safest in the long-term as a bailout procedure.

Extending the In Vivo Residence Time of Macrophage Membrane-Coated Nanoparticles through Genetic Modification.

Nanoparticles coated with natural cell membranes have emerged as a promising class of biomimetic nanomedicine with significant clinical potential. Among them, macrophage membrane-coated nanoparticles hold particular appeal due to their versatility in drug delivery and biological neutralization applications. This study employs a genetic engineering approach to enhance their in vivo residence times, aiming to further improve their performance. Specifically, macrophages are engineered to express proline-alanine-serine (PAS) peptide chains, which provide additional protection against opsonization and phagocytosis. The resulting modified nanoparticles demonstrate prolonged residence times when administered intravenously or introduced intratracheally, surpassing those coated with the wild-type membrane. The longer residence times also contribute to enhanced nanoparticle efficacy in inhibiting inflammatory cytokines in mouse models of lipopolysaccharide-induced lung injury and sublethal endotoxemia, respectively. This study underscores the effectiveness of genetic modification in extending the in vivo residence times of macrophage membrane-coated nanoparticles. This approach can be readily extended to modify other cell membrane-coated nanoparticles toward more favorable biomedical applications.

The Clinical Impact of Thoracic Endovascular Aortic Repair in the Management of Thoracic Aortic Diseases.

PURPOSE: Thoracic endovascular aortic repair (TEVAR) has been described to be superior to an open surgical approach, and previous studies have found superiority in TEVAR by reducing overall morbidity and mortality rates. This study aimed to describe the outcomes of TEVAR for patients with thoracic aortic disease at a high complexity. MATERIALS AND METHODS: Descriptive study, developed by a retrospective review of a prospectively collected database. Patients aged above 18 years who underwent TEVAR between 2012 and 2022 were included. Patient demographics, perioperative data, surgical outcomes, morbidity, and mortality were described. Statistical and multivariate analyses were made. Statistical significance was reached when p values were <0.05. RESULTS: A total of 66 patients were included. Male patients were 60.61% and the mean age was 69.24 years. Associated aortic diseases were aneurysms (68.18%), ulcer-related (4.55%), intramural-related hematoma (7.58%), trauma-related pathology (1.52%), and aortic dissection (30.30%). The mean hospital stay was 18.10 days, and intensive care unit was required for 98.48%. At 30 days, the mortality rate was 10.61% and the reintervention rate was 21.21%. Increased intraoperative blood loss (p=0.001) and male sex (p=0.04) showed statistical relationship with mortality. Underweight patients have 6.7 and 11.4 times more risk of complications and endoleak compared with higher body mass index values (p=0.04, 95% confidence interval [CI]=0.82-7.21) and (p=0.02, 95% CI=1.31-12.57), respectively. CONCLUSION: Thoracic endovascular aortic repair seems to be a feasible option for patients with thoracic aortic pathologies, with adequate rates of mortality and morbidity. Underweight patients seem to have an increased risk of overall morbidity and increased risk for endoleak. Further prospective studies are needed to prove our results. CLINICAL IMPACT: Obesity and BMI are widely studied in the surgical literature. According to our study, there is a paradox regarding the outcomes of patients treated with TEVAR in terms of postoperative complications and mortality related to the body mass index. And shouldn't be considered as a high-risk feature in terms of postoperative morbidity and mortality in this procedure.

Variations in clinical course and surgical outcomes of acute appendicitis during COVID-19 Pandemic: a multicenter cohort study.

BACKGROUND: COVID-19 pandemic has led to changes in the presentation and treatment of surgical pathologies. Therefore, we aim to describe the influence of the COVID-19 pandemic on the clinical presentation and management of acute appendicitis (AAp) and its surgical outcomes. STUDY DESIGN: A multicenter cohort study with prospectively collected databases. Three high-volume centers were included and all patients over 18 years of age who underwent appendectomy for AAp were included. Multiple logistic regression and multinomial logistic regression were performed, and odds ratio, relative risk, and B-coefficient were reported when appropriate, statistical significance was reached with p-values < 0.05. RESULTS: 1.468 patients were included (709 in the pre-pandemic group and 759 in the COVID-19 group). Female patients constituted 51.84%. Mean age was 38.13 ± 16.96 years. Mean Alvarado's score was 7.01 ± 1.59 points. Open surgical approach was preferred in 90.12%. Conversion rate of 1.29%. Mortality rate was 0.75%. There was an increase of perforated and localized peritonitis (p 0.01) in the COVID-19 group. Presence of any postoperative complication (p 0.00), requirement of right colectomy and ileostomy (p 0.00), and mortality (p 0.04) were higher in the COVID-19 group. Patients in the pre-pandemic group have a lesser risk of mortality (OR 0.14, p 0.02, 95% CI 0.02-0.81) and a lesser relative risk of having complicated appendicitis (RR 0.68, p 0.00, 95% CI 0.54-0.86). CONCLUSION: Complicated appendicitis was an unexpected consequence of the COVID-19 pandemic, due to surgical consultation delay, increased rates of morbidity, associated procedures, and mortality, influencing the clinical course and surgical outcomes of patients with AAp.

Outcomes after Frey's procedure for chronic pancreatitis: a 8-year single-center experience in Colombia.

BACKGROUND: Chronic pancreatitis is an inflammatory disease characterized by irreversible morphological changes due to chronic pancreatic fibrosis. The treatment goals are to relieve pain, preserve function, and prevent further pathological consequences. Endoscopic treatment, surgery, or both are options for untreatable pain or suspected malignancy. Frey procedure is a reasonable surgical intervention because of its hybrid character, combining resection and drainage. Unfortunately, there is limited information about the outcomes of this procedure in Latin America, and few cases described in Colombia. This study aims to describe the experience of a pancreatic surgery reference center in the management of patients undergoing Frey's surgery for chronic pancreatitis. METHODS: A retrospective review of a prospectively collected database of patients who underwent a Frey procedure due to chronic pancreatitis between January 2014 to February 2022 in a hospital in Bogotá, Colombia, was made. A demographic, clinical, and postoperative outcome description was performed. Mann-Whitney Willcoxon test was performed between operative variables and long-term outcomes. RESULTS: Eighteen patients met the inclusion criteria. 55.5% of patients were male. Chronic pancreatitis etiology in most cases (83.3% n = 15) was idiopathic. The median duration of symptoms and chronic pancreatitis diagnosis before surgery was 6.15 months (IQR 5;97). Overall morbidity was 38.88%. One patient died at 30 days of follow-up. The median follow-up time was 42.5 (IQR 19;65 months). The median pain reduction was 3 points according to the visual analog score. Six patients were diagnosed with malignant conditions after surgery (mean 27.8 ± 7.5 months). Wirsung's duct size was statistically related with malignancy presentation after Frey's procedure (Z = 2.54; P = 0.01). CONCLUSION: According to our data, Frey's procedure remains safe and feasible, with acceptable outcomes in terms of pain relief and pancreatic function. The study confirms the importance of a longstanding follow-up due to an inherent risk of pancreatic malignancy. Our data suggest that pancreatic duct size could be related with the malignancy diagnosis after Frey's procedure; however, further prospective studies with a larger sample size would be helpful to confirm these results.

The Guanine Nucleotide Exchange Factor GBF1 Participates in Rotavirus Replication.

Cellular and viral factors participate in the replication cycle of rotavirus. We report that the guanine nucleotide exchange factor GBF1, which activates the small GTPase Arf1 to induce COPI transport processes, is required for rotavirus replication since knocking down GBF1 expression by RNA interference or inhibiting its activity by treatment with brefeldin A (BFA) or Golgicide A (GCA) significantly reduces the yield of infectious viral progeny. This reduction in virus yield was related to a block in virus assembly, since in the presence of either BFA or GCA, the assembly of infectious mature triple-layered virions was significantly prevented and only double-layered particles were detected. We report that the catalytic activity of GBF1, but not the activation of Arf1, is essential for the assembly of the outer capsid of rotavirus. We show that both BFA and GCA, as well as interfering with the synthesis of GBF1, alter the electrophoretic mobility of glycoproteins VP7 and NSP4 and block the trimerization of the virus surface protein VP7, a step required for its incorporation into virus particles. Although a posttranslational modification of VP7 (other than glycosylation) could be related to the lack of trimerization, we found that NSP4 might also be involved in this process, since knocking down its expression reduces VP7 trimerization. In support, recombinant VP7 protein overexpressed in transfected cells formed trimers only when cotransfected with NSP4.IMPORTANCE Rotavirus, a member of the family Reoviridae, is the major cause of severe diarrhea in children and young animals worldwide. Despite significant advances in the characterization of the biology of this virus, the mechanisms involved in morphogenesis of the virus particle are still poorly understood. In this work, we show that the guanine nucleotide exchange factor GBF1, relevant for COPI/Arf1-mediated cellular vesicular transport, participates in the replication cycle of the virus, influencing the correct processing of viral glycoproteins VP7 and NSP4 and the assembly of the virus surface proteins VP7 and VP4.

Actin-Dependent Nonlytic Rotavirus Exit and Infectious Virus Morphogenetic Pathway in Nonpolarized Cells.

During the late stages of rotavirus morphogenesis, the surface proteins VP4 and VP7 are assembled onto the previously structured double-layered virus particles to yield a triple-layered, mature infectious virus. The current model for the assembly of the outer capsid is that it occurs within the lumen of the endoplasmic reticulum. However, it has been shown that VP4 and infectious virus associate with lipid rafts, suggesting that the final assembly of the rotavirus spike protein VP4 involves a post-endoplasmic reticulum event. In this work, we found that the actin inhibitor jasplakinolide blocks the cell egress of rotavirus from nonpolarized MA104 cells at early times of infection, when there is still no evidence of cell lysis. These findings contrast with the traditional assumption that rotavirus is released from nonpolarized cells by a nonspecific mechanism when the cell integrity is lost. Inspection of the virus present in the extracellular medium by use of density flotation gradients revealed that a fraction of the released virus is associated with low-density membranous structures. Furthermore, the intracellular localization of VP4, its interaction with lipid rafts, and its targeting to the cell surface were shown to be prevented by jasplakinolide, implying a role for actin in these processes. Finally, the VP4 present at the plasma membrane was shown to be incorporated into the extracellular infectious virus, suggesting the existence of a novel pathway for the assembly of the rotavirus spike protein.IMPORTANCE Rotavirus is a major etiological agent of infantile acute severe diarrhea. It is a nonenveloped virus formed by three concentric layers of protein. The early stages of rotavirus replication, including cell attachment and entry, synthesis and translation of viral mRNAs, replication of the genomic double-stranded RNA (dsRNA), and the assembly of double-layered viral particles, have been studied widely. However, the mechanisms involved in the later stages of infection, i.e., viral particle maturation and cell exit, are less well characterized. It has been assumed historically that rotavirus exits nonpolarized cells following cell lysis. In this work, we show that the virus exits cells by a nonlytic, actin-dependent mechanism, and most importantly, we describe that VP4, the spike protein of the virus, is present on the cell surface and is incorporated into mature, infectious virus, indicating a novel pathway for the assembly of this protein.

Rotavirus entry: a deep journey into the cell with several exits.

Rotaviruses are the leading etiological agents of acute gastroenteritis in infants and young children worldwide. These nonenveloped viruses enter cells using different types of endocytosis and, depending on the virus strain, travel to different endosomal compartments before exiting to the cytosolic space. In this Gem, we review the viral and cellular factors involved in the different stages of a productive virus cell entry and share with the readers the journey that we have taken into the cell to learn about virus entry.

Genome-wide RNAi screen reveals a role for the ESCRT complex in rotavirus cell entry.

Rotavirus (RV) is the major cause of childhood gastroenteritis worldwide. This study presents a functional genome-scale analysis of cellular proteins and pathways relevant for RV infection using RNAi. Among the 522 proteins selected in the screen for their ability to affect viral infectivity, an enriched group that participates in endocytic processes was identified. Within these proteins, subunits of the vacuolar ATPase, small GTPases, actinin 4, and, of special interest, components of the endosomal sorting complex required for transport (ESCRT) machinery were found. Here we provide evidence for a role of the ESCRT complex in the entry of simian and human RV strains in both monkey and human epithelial cells. In addition, the ESCRT-associated ATPase VPS4A and phospholipid lysobisphosphatidic acid, both crucial for the formation of intralumenal vesicles in multivesicular bodies, were also found to be required for cell entry. Interestingly, it seems that regardless of the molecules that rhesus RV and human RV strains use for cell-surface attachment and the distinct endocytic pathway used, all these viruses converge in early endosomes and use multivesicular bodies for cell entry. Furthermore, the small GTPases RHOA and CDC42, which regulate different types of clathrin-independent endocytosis, as well as early endosomal antigen 1 (EEA1), were found to be involved in this process. This work reports the direct involvement of the ESCRT machinery in the life cycle of a nonenveloped virus and highlights the complex mechanism that these viruses use to enter cells. It also illustrates the efficiency of high-throughput RNAi screenings as genetic tools for comprehensively studying the interaction between viruses and their host cells.

Rotaviruses reach late endosomes and require the cation-dependent mannose-6-phosphate receptor and the activity of cathepsin proteases to enter the cell.

UNLABELLED: Rotaviruses (RVs) enter cells through different endocytic pathways. Bovine rotavirus (BRV) UK uses clathrin-mediated endocytosis, while rhesus rotavirus (RRV) employs an endocytic process independent of clathrin and caveolin. Given the differences in the cell internalization pathway used by these viruses, we tested if the intracellular trafficking of BRV UK was the same as that of RRV, which is known to reach maturing endosomes (MEs) to infect the cell. We found that BRV UK also reaches MEs, since its infectivity depends on the function of Rab5, the endosomal sorting complex required for transport (ESCRT), and the formation of endosomal intraluminal vesicles (ILVs). However, unlike RRV, the infectivity of BRV UK was inhibited by knocking down the expression of Rab7, indicating that it has to traffic to late endosomes (LEs) to infect the cell. The requirement for Rab7 was also shared by other RV strains of human and porcine origin. Of interest, most RV strains that reach LEs were also found to depend on the activities of Rab9, the cation-dependent mannose-6-phosphate receptor (CD-M6PR), and cathepsins B, L, and S, suggesting that cellular factors from the trans-Golgi network (TGN) need to be transported by the CD-M6PR to LEs to facilitate RV cell infection. Furthermore, using a collection of UK × RRV reassortant viruses, we found that the dependence of BRV UK on Rab7, Rab9, and CD-M6PR is associated with the spike protein VP4. These findings illustrate the elaborate pathway of RV entry and reveal a new process (Rab9/CD-M6PR/cathepsins) that could be targeted for drug intervention. IMPORTANCE: Rotavirus is an important etiological agent of severe gastroenteritis in children. In most instances, viruses enter cells through an endocytic pathway that delivers the viral particle to vesicular organelles known as early endosomes (EEs). Some viruses reach the cytoplasm from EEs, where they start to replicate their genome. However, other viruses go deeper into the cell, trafficking from EEs to late endosomes (LEs) to disassemble and reach the cytoplasm. In this work, we show that most RV strains have to traffic to LEs, and the transport of endolysosomal proteases from the Golgi complex to LEs, mediated by the mannose-6-phosphate receptor, is necessary for the virus to exit the vesicular compartment and efficiently start viral replication. We also show that this deep journey into the cell is associated with the virus spike protein VP4. These findings illustrate the elaborate pathway of RV entry that could be used for drug intervention.

Delayed gastric emptying after pancreatoduodenectomy: an analysis of risk factors.

BACKGROUND: Delayed gastric emptying (DGE) is a frequent complication after pancreatoduodenectomy. Preoperative factors are limited and controversial. This study aims to identify associated factors related to this complication in the Colombian population. METHODS: A retrospective review of a prospectively collected database was conducted. All patients over 18 years of age who underwent pancreaticoduodenectomy were included. Associations with DGE syndrome were evaluated with logistic regression analysis, Odds ratio, and b-coefficient were provided when appropriate. RESULTS: 205 patients were included. Male patients constituted 54.15% (n = 111). 53 patients (25.85%) were diagnosed with DGE syndrome. Smoking habit (OR 17.58 p 0.00 95% CI 7.62-40.51), hydromorphone use > 0.6 mg/daily (OR 11.04 p 0.03 95% CI 1.26-96.66), bilirubin levels > 6 mg/dL (OR 2.51 p 0.02 95% CI 1.12-5.61), and pancreatic fistula type B (OR 2.72 p 0.02 CI 1.74-10.00). DISCUSSION: Smoking history, opioid use (hydromorphone > 0.6 mg/Daily), type B pancreatic fistula, and bilirubin levels > 6 mg/dL should be considered as risk factors for DGE.

Postoperative pain in transabdominal preperitoneal laparoscopic hernia repair with staple fixation versus self-fixation mesh.

Background: The mesh fixation method is one of the multiple factors associated with chronic postoperative pain in inguinal hernia surgery. The aim of this study is to evaluate postoperative pain associated with the two available fixation strategies (staple fixation versus self-fixating mesh) used in our field. Methods: We designed an observational study with retrospective cohorts to analyze postoperative pain in patients who underwent a laparoscopic transabdominal preperitoneal inguinal hernia repair with a self-fixating mesh or staple fixation, which are the two available techniques in our field. A total of 296 patients who met the inclusion criteria were included between January 2014 and October 2021. Results: The evaluated patients' median age was 66.0 (interquartile range (IQR): 20.75) years and were predominantly male (70.13 %). The proportion of participants with chronic pain was 3.20 % in the staple fixation group and 0 % in the self-fixating mesh group, with no statistically significant differences. On the other hand, recurrency in the staple fixation group was 2.28 % versus 3.90 % in the self-fixating mesh group, without statistically significant differences. Conclusions: Self-fixating meshes have a trend towards smaller proportion of chronic pain and similar proportions of recurrence; therefore, they seem to be the best fixation method between the two mechanisms that are available in our field to prevent postoperative chronic pain.

Heterogeneous brain region-specific responses to astrocytic mitochondrial DNA damage in mice.

Astrocytes display context-specific diversity in their functions and respond to noxious stimuli between brain regions. Astrocytic mitochondria have emerged as key players in governing astrocytic functional heterogeneity, given their ability to dynamically adapt their morphology to regional demands on ATP generation and Ca2+ buffering functions. Although there is reciprocal regulation between mitochondrial dynamics and mitochondrial Ca2+ signaling in astrocytes, the extent of this regulation in astrocytes from different brain regions remains unexplored. Brain-wide, experimentally induced mitochondrial DNA (mtDNA) loss in astrocytes showed that mtDNA integrity is critical for astrocyte function, however, possible diverse responses to this noxious stimulus between brain areas were not reported in these experiments. To selectively damage mtDNA in astrocytes in a brain-region-specific manner, we developed a novel adeno-associated virus (AAV)-based tool, Mito-PstI expressing the restriction enzyme PstI, specifically in astrocytic mitochondria. Here, we applied Mito-PstI to two brain regions, the dorsolateral striatum and dentate gyrus, and we show that Mito-PstI induces astrocytic mtDNA loss in vivo, but with remarkable brain-region-dependent differences on mitochondrial dynamics, Ca2+ fluxes, and astrocytic and microglial reactivity. Thus, AAV-Mito-PstI is a novel tool to explore the relationship between astrocytic mitochondrial network dynamics and astrocytic mitochondrial Ca2+ signaling in a brain-region-selective manner.

Heterogeneous brain region-specific responses to astrocytic mitochondrial DNA damage in mice.

Astrocytes use Ca 2+ signals to regulate multiple aspects of normal and pathological brain function. Astrocytes display context-specific diversity in their functions, and in their response to noxious stimuli between brain regions. Indeed, astrocytic mitochondria have emerged as key players in governing astrocytic functional heterogeneity, given their ability to dynamically adapt their morphology to regional demands on their ATP generation and Ca 2+ buffering functions. Although there is reciprocal regulation between mitochondrial dynamics and mitochondrial Ca 2+ signaling in astrocytes, the extent of this regulation into the rich diversity of astrocytes in different brain regions remains largely unexplored. Brain-wide, experimentally induced mitochondrial DNA (mtDNA) loss in astrocytes showed that mtDNA integrity is critical for proper astrocyte function, however, few insights into possible diverse responses to this noxious stimulus from astrocytes in different brain areas were reported in these experiments. To selectively damage mtDNA in astrocytes in a brain-region-specific manner, we developed a novel adeno-associated virus (AAV)-based tool, Mito-PstI, which expresses the restriction enzyme PstI, specifically in astrocytic mitochondria. Here, we applied Mito-PstI to two distinct brain regions, the dorsolateral striatum, and the hippocampal dentate gyrus, and we show that Mito-PstI can induce astrocytic mtDNA loss in vivo , but with remarkable brain-region-dependent differences on mitochondrial dynamics, spontaneous Ca 2+ fluxes and astrocytic as well as microglial reactivity. Thus, AAV-Mito-PstI is a novel tool to explore the relationship between astrocytic mitochondrial network dynamics and astrocytic mitochondrial Ca 2+ signaling in a brain-region-selective manner.

Case Report: ALPPS hepatectomy, an alternative to liver transplantation in central PRETEXT III hepatoblastomas: a case series.

Introduction: Hepatoblastoma is the most common malignant primary liver tumor in the pediatric population, accounting for 67% of cases in the United States. Surgical resection is the only curative treatment option; however, it can be performed in only 10% of patients with primary tumors. The two most common limitations for resection are the need for extensive resections and tumors in central locations. The therapeutic hypertrophy of healthy tissue achieved with ALPPS (Associating Liver Partition and Portal vein ligation for Staged Hepatectomy) enables larger resections and has been successfully employed in the pediatric population in recent years. Objective: To present three cases of patients with centrally located PRETEXT II or III hepatoblastomas who underwent ALPPS procedure as a viable therapeutic alternative to liver transplantation. Discussion and results: Central PRETEXT III hepatoblastomas are typically indications for liver transplantation. Transplantation offers high five-year survival rates (73%). However, the associated morbidity, healthcare system costs, and limited availability make it necessary to explore alternative options. Series have reported the successful application of the ALPPS procedure in PRETEXT II and PRETEXT III hepatoblastomas in other locations. Therapeutically induced hypertrophy, characterized by an increase in the volume of healthy tissue in unaffected lobes or segments, enabled the resection of previously deemed unresectable lesions. The patients experienced uncomplicated postoperative courses and expected reduction in tumor markers. Chemotherapy selection followed the guidelines outlined in Block C of the SIOPEL IV protocol. Conclusions: ALPPS hepatectomy is a viable therapeutic option for patients with centrally located PRETEXT III or II hepatoblastomas.

Case Report: A rare instance of acute appendicitis induced by Balantidium Coli parasitic infection.

Introduction: Acute appendicitis secondary to parasitic infections is uncommon, being detected in less than 1% of cases. Balantidium coli is a parasite found in pigs and primates with zoonotic potential. To date, only three cases of acute appendicitis induced by this parasite have been documented globally. Case: A 7-year-old female patient, who consumed pork daily, presented to the emergency department with a one-day history of abdominal pain in the lower quadrants, described as colic-like, alongside abdominal distension. Initial abdominal radiography led to a diagnosis of intestinal obstruction. Conservative management without therapeutic response necessitated referral to a higher complexity center. Upon admission, an abdominal computed tomography scan diagnosed acute appendicitis and secondary ileus. During surgical intervention, an appendiceal phlegmon formed by loops of the small intestine was mechanically released, revealing a perforated appendix with extensive fecal peritoneal contamination. Pathological analysis identified an inflammatory infiltrate and the presence of Balantidium coli trophozoites. Medical treatment included Piperacillin-Tazobactam and Metronidazole. The patient was discharged after 10 days of medical treatment. Discussion: Acute appendicitis caused by Balantidium coli is a rare occurrence. It is crucial to identify parasites in pathological samples due to their impact on postoperative management. The close contact between humans and pigs, especially in developing countries, suggests that the prevalence of parasitic infection and colonization by Balantidium coli may be higher than currently recognized. Regarding the identification of this patient's specific exposure, the regular consumption of pork suggests the hypothesis that improper processing is linked to the acquisition of the parasitic infection.

Leveraging the Aggregated Protein Dye YAT2150 for Malaria Chemotherapy.

Background/Objectives: YAT2150 is a first-in-class antiplasmodial compound that has been recently proposed as a new interesting drug for malaria therapy. Methods/Results: The fluorescence of YAT2150 rapidly increases upon its entry into Plasmodium, a property that can be of use for the design of highly sensitive diagnostic approaches. YAT2150 blocks the in vitro development of the ookinete stage of Plasmodium and, when added to an infected blood meal, inhibits oocyst formation in the mosquito. Thus, the compound could possibly contribute to future transmission-blocking antimalarial strategies. Cell influx/efflux studies in Caco-2 cells suggest that YAT2150 is internalized by endocytosis and also through the OATP2B1 transporter, whereas its main export route would be via OSTα. YAT2150 has an overall favorable drug metabolism and pharmacokinetics profile, and its moderate cytotoxicity can be significantly reduced upon encapsulation in immunoliposomes, which leads to a dramatic increase in the drug selectivity index to values close to 1000. Although YAT2150 binds amyloid-forming peptides, its in vitro fluorescence emission is stronger upon association with peptides that form amorphous aggregates, suggesting that regions enriched in unstructured proteins are the preferential binding sites of the drug inside Plasmodium cells. The reduction of protein aggregation in the parasite after YAT2150 treatment, which has been suggested to be directly related to the drug's mode of action, is also observed following treatment with quinoline antimalarials like chloroquine and primaquine. Conclusions: Altogether, the data presented here indicate that YAT2150 can represent the spearhead of a new family of compounds for malaria diagnosis and therapy due to its presumed novel mode of action based on the interaction with functional protein aggregates in the pathogen.

Endovascular approach of hepatic artery pseudoaneurysm after Whipple procedure: Case report and literature review.

INTRODUCTION AND IMPORTANCE: Pseudoaneurysms after pancreatoduodenectomy are an uncommon complication, but they are associated with life-threatening outcomes in up to 50 % due to the development of postoperative bleeding. They usually result as a consequence of local inflammatory processes, such as pancreatic fistula or intra-abdominal collections. The cornerstones of treatment are thus intraoperative management and early identification of the complication. CASE PRESENTATION: We present a 62-year-old female patient in postoperative pancreatoduodenectomy due to a periampullary tumor, that presented upper gastrointestinal bleeding which required multiple transfusions. During hospitalization, the patient presented a refractory hypovolemic shock to conservative measures. It was documented intra-abdominal hemorrhage due to hepatic artery pseudoaneurysm that required endovascular management with common hepatic artery embolization, with successful bleeding control. CLINICAL DISCUSSION: Pseudoaneurysms are the result of tissue damage after surgery. The usual clinical presentation is upper gastrointestinal bleeding unresponsive to conservative treatment that results in hemodynamic instability due to hypovolemic shock. Prevention is currently based on preoperative and intraoperative measures such as nutritional repletion, vessel protection, adequate hemostasis, and prevention and treatment of pancreatic leak and abdominal infection. Once documented, treatment can be endovascular or surgical. CONCLUSION: The formation of pseudoaneurysms after pancreaticoduodenectomy is an uncommon and challenging complication. Early diagnosis, risk factor detection and a combined multidisciplinary approach lead to better outcomes, avoiding open surgical procedures that can increase morbidity and mortality rates.

Replication of the rotavirus genome requires an active ubiquitin-proteasome system.

Here we show that the ubiquitin-proteasome system is required for the efficient replication of rotavirus RRV in MA104 cells. The proteasome inhibitor MG132 decreased the yield of infectious virus under conditions where it severely reduces the synthesis of not only viral but also cellular proteins. Addition of nonessential amino acids to the cell medium restored both viral protein synthesis and cellular protein synthesis, but the production of progeny viruses was still inhibited. In medium supplemented with nonessential amino acids, we showed that MG132 does not affect rotavirus entry but inhibits the replication of the viral genome. It was also shown that it prevents the efficient incorporation into viroplasms of viral polymerase VP1 and the capsid proteins VP2 and VP6, which could explain the inhibitory effect of MG132 on genome replication and infectious virus yield. We also showed that ubiquitination is relevant for rotavirus replication since the yield of rotavirus progeny in cells carrying a temperature-sensitive mutation in the E1 ubiquitin-activating enzyme was reduced at the restrictive temperature. In addition, overexpression of ubiquitin in MG132-treated MA104 cells partially reversed the effect of the inhibitor on virus yield. Altogether, these data suggest that the ubiquitin-proteasome (UP) system has a very complex interaction with the rotavirus life cycle, with both the ubiquitination and proteolytic activities of the system being relevant for virus replication.

Trans-gastric and trans-abdominal percutaneous drainage of acute peripancreatic fluid infected collections: A retrospective analysis.

Background: Acute pancreatitis is one of the most common gastrointestinal diseases. Approximately 20% of the patients develop peripancreatic collections. Step-up management it's now the best approach with less rate of morbidity and mortality compared with open or minimally invasive surgery. Percutaneous management could reach a success rate between 50 and 76%. Our study shows the outcomes of trans-gastric versus transabdominal percutaneous drainage in cases of acute peripancreatic fluid infected collections in the absence of interventionist endoscopy. Methods: A retrospective review of a prospectively collected database was conducted. All the patients older than 18 years old that underwent percutaneous drainage between January 2010-December 2021 were included. Analysis and description of outcomes such as mortality, complications, and avoidance of surgical procedures was performed. Results: 18 patients underwent percutaneous drainage. 66.67% of patients were male. Mean age was 52.55 ± 22.06 years. Mean weight was 74.43 ± 15.25 kg. Mean size of peripancreatic collections 118.4 ± 49.12 mm. Wall-off necrosis was present in 33.33%. Trans-gastric approach was performed in 50% of the cases, the rest was trans-abdominal. No mortality was evidenced after 30 days of follow up. After trans-gastric percutaneous drainage, all patients avoided surgical open or laparoscopic procedure. Conclusion: Standardized step-up approach shows increased rates of success in percutaneous drainage of peripancreatic collections. Our case series shows a high rate of success in terms of avoidance any surgical procedure with no mortality after trans-abdominal and trans-gastric percutaneous drainage. Nevertheless, further prospective studies with higher sample size are needed.