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L. donovani and L. infantum infections are associated with a broad clinical spectrum, ranging from asymptomatic cases to visceral leishmaniasis (VL) with high mortality rates. Clinical manifestations such as post-kala-azar dermal leishmaniasis (PKDL) and visceral leishmaniasis-associated hemophagocytic lymphohistiocytosis-mimic (VL-associated HLH-mimic) further contribute to the diversity of clinical manifestations. These clinical variations are intricately influenced by the complex interplay between the host's immune response and the parasite's escape mechanisms. This narrative review aims to elucidate the underlying immunological mechanisms associated with each clinical manifestation, drawing from published literature within the last 5 years. Specific attention is directed toward viscerotropic Leishmania sinfection in patients with inborn errors of immunity and acquired immunodeficiencies. In VL, parasites exploit various immune evasion mechanisms, including immune checkpoints, leading to a predominantly anti-inflammatory environment that favors parasite survival. Conversely, nearly 70% of individuals are capable of mounting an effective pro-inflammatory immune response, forming granulomas that contain the parasites. Despite this, some patients may experience reactivation of the disease upon immunosuppression, challenging current understandings of parasite eradication. Individuals living with HIV and those with inborn errors of immunity present a more severe course of infection, often with higher relapse rates. Therefore, it is crucial to exclude both primary and acquired immune deficiencies in patients presenting disease relapse and VL-associated HLH-mimic. The distinction between VL and HLH can be challenging due to clinical similarities, suggesting that the nosological entity known as VL-associated HLH may represent a severe presentation of symptomatic VL and it should be considered more accurate referring to this condition as VL-associated HLH-mimic. Consequently, excluding VL in patients presenting with HLH is essential, as appropriate antimicrobial therapy can reverse immune dysregulation. A comprehensive understanding of the immune-host interaction underlying Leishmania infection is crucial for formulating effective treatment and preventive strategies to mitigate the disease burden. [ABSTRACT FROM AUTHOR]

Purpose: Body composition measurements from routine abdominal CT can yield personalized risk assessments for asymptomatic and diseased patients. In particular, attenuation and volume measures of muscle and fat are associated with important clinical outcomes, such as cardiovascular events, fractures, and death. This study evaluates the reliability of an Internal tool for the segmentation of muscle and fat (subcutaneous and visceral) as compared to the well-established public TotalSegmentator tool. Methods: We assessed the tools across 900 CT series from the publicly available SAROS dataset, focusing on muscle, subcutaneous fat, and visceral fat. The Dice score was employed to assess accuracy in subcutaneous fat and muscle segmentation. Due to the lack of ground truth segmentations for visceral fat, Cohen's Kappa was utilized to assess segmentation agreement between the tools. Results: Our Internal tool achieved a 3% higher Dice (83.8 vs. 80.8) for subcutaneous fat and a 5% improvement (87.6 vs. 83.2) for muscle segmentation, respectively. A Wilcoxon signed-rank test revealed that our results were statistically different with p < 0.01. For visceral fat, the Cohen's Kappa score of 0.856 indicated near-perfect agreement between the two tools. Our internal tool also showed very strong correlations for muscle volume (R 2 =0.99), muscle attenuation (R 2 =0.93), and subcutaneous fat volume (R 2 =0.99) with a moderate correlation for subcutaneous fat attenuation (R 2 =0.45). Conclusion: Our findings indicated that our Internal tool outperformed TotalSegmentator in measuring subcutaneous fat and muscle. The high Cohen's Kappa score for visceral fat suggests a reliable level of agreement between the two tools. These results demonstrate the potential of our tool in advancing the accuracy of body composition analysis. [ABSTRACT FROM AUTHOR]

Abstract Background Leishmania infantum is endemic in the Mediterranean region, presenting mostly as visceral leishmaniasis (VL). In Portugal, reporting of VL cases to public health authorities is mandatory, but significant underreporting is likely. This study aimed to describe the epidemiological and clinical aspects of the VL cases diagnosed in hospitals of the Portuguese National Health Service (NHS), between 2010 and 2020. Methods Collaboration was requested to every hospital of the Portuguese NHS in Mainland Portugal. Cases were screened through a search of diagnostic discharge codes or, if not available, by a search of positive laboratory results for Leishmania infection. Sociodemographic and clinical data was retrieved from medical records. Simultaneously, the National Health authority was contacted to request access to data of notified cases of VL between 2010 and 2020. Descriptive, hypothesis testing and multiple binary logistic regression models were performed. Results A total of 221 VL cases were identified. A significant increase in estimated national incidence was seen in the years after 2016 (P = 0.030). VL was predominantly diagnosed in people living with HIV (PLWH) and in children (representing around 60% of the new cases), but the outcome was generally poorer in non-HIV patients with associated immunosuppression, with significantly lower rates of clinical improvement at 7 (P = 0.003) and 30 days (P = 0.008) after treatment. Atypical presentations, with gastrointestinal and/or respiratory involvement, were seen in 8.5% of VL cases. Hemophagocytic lymphohistiocytosis was diagnosed in 40.0% of children under 5 years of age. Only 49.7% of incident VL cases were reported. Simultaneous involvement of the skin was confirmed in 5.9% of patients. Conclusions VL presents a continuing threat in Portugal, especially to PLWH and children, and an increasing threat to other immunosuppressed groups. Recent increases in incidence should be closely monitored to allow prompt interventions. Programs to control the disease should focus on providing tools for earlier diagnosis and on reducing underreporting and promoting an integrated surveillance of human and animal disease. These data should be combined with asymptomatic infection and vector information, following a One Health approach. Graphical Abstract

Background Obesity, especially abdominal obesity, is strongly correlated with metabolic and other health risks. Diagnosis and assessment of obesity is important in clinical and routine preventive practice. From the point of view of risk, it is necessary to distinguish not only the area of fat tissue accumulation, but also its type. Objective The aim of the study was to use a new portable abdominal bioimpedance analyzer, which is intended for the area of abdominal adipose tissue, as part of the evaluation of the body structure of a selected group of volunteers with a focus on the differentiation of subcutaneous and visceral adipose tissue and to assess its usefulness in practice. Material and Methods Body composition was analyzed using a portable abdominal bioimpedance analyzer Yscope (PA-BIA) in combination with a bioimpedance device InBody 970 (high-frequency bioelectrical impedance/HF-BIA). Eighty-three volunteers at the age of 24.92±7.24 years with representation of both sexes participated in the study. Results Abdominal fat did not differ significantly between the sexes, women reached an average value of 2.01±1.14 kg, men 2.22±1.60 kg (p>0.05). Gender differentiation was manifested in the case of visceral fat (p

The aim of this study was to analyse and compare the outcome of open surgery (OS) and endovascular repair (ER) for the treatment of visceral artery aneurysms (VAA). A systematic literature search was carried out. 25 comparative cohort studies with 4447 patients (2469 OS and 1978 ER) were included in the meta-analysis. Mortality (ER vs OS 1.8% vs 2.1%, OR.77, 95% CI [.51; 1.17], P =.23) and technical success rates (97% vs 98%, OR.50, 95% CI [.21; 1.16], P =.11) were comparable between both groups. Lower mortality rates for ER were observed for ruptured aneurysms (4.1% vs 31%, OR.43 95% CI [.13; 1.43], P =.17). Length of stay was shorter (mean difference −4.25 days, 95% CI [−5.52; −2.98], P <.00001) and 1-year reintervention rates were higher in the ER group (9% vs 5%, OR 1.55 95% CI [.58; 4.12], P =.38. The presented evidence suggests that ER should be considered a first-line treatment for VAAs, especially in an emergency setting, due to lower morbidity and comparable mortality and technical success. Follow-up should be offered to these patients due to the higher reintervention rates. Systematic review registration: PROSPERO ID 348699 [ABSTRACT FROM AUTHOR]

Pain is a major issue in healthcare throughout the world. It remains one of the major clinical issues of our time because it is a common sequela of numerous conditions, has a tremendous impact on individual quality of life, and is one of the top drivers of cost in medicine, due to its influence on healthcare expenditures and lost productivity in those affected by it. Patients and healthcare providers remain desperate to find new, safer and more effective analgesics. Growing evidence indicates that the voltage-gated sodium channel Nav1.8 plays a critical role in transmission of pain-related signals throughout the body. For that reason, this channel appears to have strong potential to help develop novel, more selective, safer, and efficacious analgesics. However, many questions related to the physiology, function, and clinical utility of Nav1.8 remain to be answered. In this article, we discuss the latest studies evaluating the role of Nav1.8 in pain, with a particular focus on visceral pain, as well as the steps taken thus far to evaluate its potential as an analgesic target. We also review the limitations of currently available studies related to this topic, and describe the next scientific steps that have already been undertaken, or that will need to be pursued, to fully unlock the capabilities of this potential therapeutic target. [ABSTRACT FROM AUTHOR]

Background: Leishmania infantum is endemic in the Mediterranean region, presenting mostly as visceral leishmaniasis (VL). In Portugal, reporting of VL cases to public health authorities is mandatory, but significant underreporting is likely. This study aimed to describe the epidemiological and clinical aspects of the VL cases diagnosed in hospitals of the Portuguese National Health Service (NHS), between 2010 and 2020. Methods: Collaboration was requested to every hospital of the Portuguese NHS in Mainland Portugal. Cases were screened through a search of diagnostic discharge codes or, if not available, by a search of positive laboratory results for Leishmania infection. Sociodemographic and clinical data was retrieved from medical records. Simultaneously, the National Health authority was contacted to request access to data of notified cases of VL between 2010 and 2020. Descriptive, hypothesis testing and multiple binary logistic regression models were performed. Results: A total of 221 VL cases were identified. A significant increase in estimated national incidence was seen in the years after 2016 (P = 0.030). VL was predominantly diagnosed in people living with HIV (PLWH) and in children (representing around 60% of the new cases), but the outcome was generally poorer in non-HIV patients with associated immunosuppression, with significantly lower rates of clinical improvement at 7 (P = 0.003) and 30 days (P = 0.008) after treatment. Atypical presentations, with gastrointestinal and/or respiratory involvement, were seen in 8.5% of VL cases. Hemophagocytic lymphohistiocytosis was diagnosed in 40.0% of children under 5 years of age. Only 49.7% of incident VL cases were reported. Simultaneous involvement of the skin was confirmed in 5.9% of patients. Conclusions: VL presents a continuing threat in Portugal, especially to PLWH and children, and an increasing threat to other immunosuppressed groups. Recent increases in incidence should be closely monitored to allow prompt interventions. Programs to control the disease should focus on providing tools for earlier diagnosis and on reducing underreporting and promoting an integrated surveillance of human and animal disease. These data should be combined with asymptomatic infection and vector information, following a One Health approach. [ABSTRACT FROM AUTHOR]

Sexual dimorphism of visceral pain has been documented in clinics and experimental animal models. Aside from hormones, emerging evidence suggests the sex-differential intrinsic neural regulation of pain generation and maintenance. According to the International Association for the Study of Pain (IASP) and the American College of Gastroenterology (ACG), up to 25% of the population have visceral pain at any one time, and in the United States 10–15 percent of adults suffer from irritable bowel syndrome (IBS). Here we examine the preclinical and clinical evidence of sex differences in visceral pain focusing on IBS, other forms of bowel dysfunction and IBS-associated comorbidities. We summarize preclinical animal models that provide a means to investigate the underlying molecular mechanisms in the sexual dimorphism of visceral pain. Neurons and nonneuronal cells (glia and immune cells) in the peripheral and central nervous systems, and the communication of gut microbiota and neural systems all contribute to sex-dependent nociception and nociplasticity in visceral painful signal processing. Emotion is another factor in pain perception and appears to have sexual dimorphism. [ABSTRACT FROM AUTHOR]

Deciphering lipid metabolism in white adipose tissue (WAT) depots during weight gain is important to understand the heterogeneity of WAT and its roles in obesity. Here, we examined the expression of key enzymes of lipid metabolism and changes in the morphology of representative visceral (epididymal) and subcutaneous (inguinal) WAT (eWAT and iWAT, respectively)-in adult male rats acclimated to cold (4 ± 1 °C) for 45 days and reacclimated to room temperature (RT, 22 ± 1 °C) for 1, 3, 7, 12, 21, or 45 days. The relative mass of both depots decreased to a similar extent after cold acclimation. However, fatty acid synthase (FAS), glucose-6-phosphate dehydrogenase (G6PDH), and medium-chain acyl-CoA dehydrogenase (ACADM) protein level increased only in eWAT, whereas adipose triglyceride lipase (ATGL) expression increased only in iWAT. During reacclimation, the relative mass of eWAT reached control values on day 12 and that of iWAT on day 45 of reacclimation. The faster recovery of eWAT mass is associated with higher expression of FAS, acetyl-CoA carboxylase (ACC), G6PDH, and ACADM during reacclimation and a delayed increase in ATGL. The absence of an increase in proliferating cell nuclear antigen suggests that the observed depot-specific mass increase is predominantly due to metabolic adjustments. In summary, this study shows a differential rate of visceral and subcutaneous adipose tissue weight regain during post-cold reacclimation of rats at RT. Faster recovery of the visceral WAT as compared to subcutaneous WAT during reacclimation at RT could be attributed to observed differences in the expression patterns of lipid metabolic enzymes. [ABSTRACT FROM AUTHOR]

L. donovani and L. infantum infections are associated with a broad clinical spectrum, ranging from asymptomatic cases to visceral leishmaniasis (VL) with high mortality rates. Clinical manifestations such as post-kala-azar dermal leishmaniasis (PKDL) and visceral leishmaniasis-associated hemophagocytic lymphohistiocytosis-mimic (VL-associated HLH-mimic) further contribute to the diversity of clinical manifestations. These clinical variations are intricately influenced by the complex interplay between the host’s immune response and the parasite’s escape mechanisms. This narrative review aims to elucidate the underlying immunological mechanisms associated with each clinical manifestation, drawing from published literature within the last 5 years. Specific attention is directed toward viscerotropic Leishmania sinfection in patients with inborn errors of immunity and acquired immunodeficiencies. In VL, parasites exploit various immune evasion mechanisms, including immune checkpoints, leading to a predominantly anti-inflammatory environment that favors parasite survival. Conversely, nearly 70% of individuals are capable of mounting an effective pro-inflammatory immune response, forming granulomas that contain the parasites. Despite this, some patients may experience reactivation of the disease upon immunosuppression, challenging current understandings of parasite eradication. Individuals living with HIV and those with inborn errors of immunity present a more severe course of infection, often with higher relapse rates. Therefore, it is crucial to exclude both primary and acquired immune deficiencies in patients presenting disease relapse and VL-associated HLH-mimic. The distinction between VL and HLH can be challenging due to clinical similarities, suggesting that the nosological entity known as VL-associated HLH may represent a severe presentation of symptomatic VL and it should be considered more accurate referring to this condition as VL-associated HLH-mimic. Consequently, excluding VL in patients presenting with HLH is essential, as appropriate antimicrobial therapy can reverse immune dysregulation. A comprehensive understanding of the immune-host interaction underlying Leishmania infection is crucial for formulating effective treatment and preventive strategies to mitigate the disease burden.

Visceral leishmaniasis (VL) is among the most neglected tropical diseases in the world. Drug cell permeability is essential for killing the intracellular residing parasites responsible for VL, making cell-permeating peptides a logical choice to address VL. Unfortunately, the limited biological stability of peptides restricts their usage. Sequence-specific oligo-N-substituted glycines ('peptoids') are a class of peptide mimics that offers an excellent alternative to peptides in terms of ease of synthesis and good biostability. We tested peptoids against the parasite Leishmania donovani in both forms, that is, intracellular amastigotes and promastigotes. N-alkyl hydrophobic chain addition (lipidation) and bromination of oligopeptoids yielded compounds with good antileishmanial activity against both forms, showing the promise of these antiparasitic peptoids as potential drug candidates to treat VL.

Aims/hypothesisSouth Asians have a two- to fivefold higher risk of developing type 2 diabetes than those of white European descent. Greater central adiposity and storage of fat in deeper or ectopic depots are potential contributing mechanisms. We collated existing and new data on the amount of subcutaneous (SAT), visceral (VAT) and liver fat in adults of South Asian and white European descent to provide a robust assessment of potential ethnic differences in these factors.MethodsWe performed a systematic review of the Embase and PubMed databases from inception to August 2021. Unpublished imaging data were also included. The weighted standardised mean difference (SMD) for each adiposity measure was estimated using random-effects models. The quality of the studies was assessed using the ROBINS-E tool for risk of bias and overall certainty of the evidence was assessed using the GRADE approach. The study was pre-registered with the OSF Registries ( https://osf.io/w5bf9 ).ResultsWe summarised imaging data on SAT, VAT and liver fat from eight published and three previously unpublished datasets, including a total of 1156 South Asian and 2891 white European men, and 697 South Asian and 2271 white European women. Despite South Asian men having a mean BMI approximately 0.5-0.7 kg/m2 lower than white European men (depending on the comparison), nine studies showed 0.34 SMD (95% CI 0.12, 0.55; I2=83%) more SAT and seven studies showed 0.56 SMD (95% CI 0.14, 0.98; I2=93%) more liver fat, but nine studies had similar VAT (-0.03 SMD; 95% CI -0.24, 0.19; I2=85%) compared with their white European counterparts. South Asian women had an approximately 0.9 kg/m2 lower BMI but 0.31 SMD (95% CI 0.14, 0.48; I2=53%) more liver fat than their white European counterparts in five studies. Subcutaneous fat levels (0.03 SMD; 95% CI -0.17, 0.23; I2=72%) and VAT levels (0.04 SMD; 95% CI -0.16, 0.24; I2=71%) did not differ significantly between ethnic groups in eight studies of women.Conclusions/interpretationSouth Asian men and women appear to store more ectopic fat in the liver compared with their white European counterparts with similar BMI levels. Given the emerging understanding of the importance of liver fat in diabetes pathogenesis, these findings help explain the greater diabetes risks in South Asians.FundingThere was no primary direct funding for undertaking the systematic review and meta-analysis.

BackgroundIn line with movement restrictions and physical distancing essential for the control of the COVID-19 pandemic, WHO recommended postponement of all neglected tropical disease (NTD) control activities that involve community-based surveys, active case finding, and mass drug administration in April, 2020. Following revised guidance later in 2020, and after interruptions to NTD programmes of varying lengths, NTD programmes gradually restarted in the context of an ongoing pandemic. However, ongoing challenges and service gaps have been reported. This study aimed to evaluate the potential effect of the programmatic interruptions and strategies to mitigate this effect.MethodsFor seven NTDs, namely soil-transmitted helminths, schistosomiasis, lymphatic filariasis, onchocerciasis, trachoma, visceral leishmaniasis, and human African trypanosomiasis, we used mathematical transmission models to simulate the effect of programme interruptions on the dynamics of each of these diseases in different endemic settings. We also explored the potential benefit of implementing mitigation strategies, primarily in terms of minimising the delays to control targets.FindingsWe show that the effect of the COVID-19-induced interruption in terms of delay to achieving elimination goals might in some cases be much longer than the duration of the interruption. For schistosomiasis, onchocerciasis, trachoma, and visceral leishmaniasis, a mean delay of 2-3 years for a 1-year interruption is predicted in areas of highest prevalence. We also show that these delays can largely be mitigated by measures such as additional mass drug administration or enhanced case-finding.InterpretationThe COVID-19 pandemic has brought infectious disease control to the forefront of global consciousness. It is essential that the NTDs, so long neglected in terms of research and financial support, are not overlooked, and remain a priority in health service planning and funding.FundingBill & Melinda Gates Foundation, Medical Research Council, and the UK Foreign, Commonwealth & Development Office.

Visceral leishmaniasis (VL), often referred to as kala-azar, is quite rare in developed countries during pregnancy. Only few studies have evaluated its impact on perinatal outcome. It is caused primarily by Leishmania donovani or Leishmania infantum and presents with a wide spectrum of clinical manifestations from cutaneous ulcers to multisystem disease. Differential diagnosis is challenging as symptoms and signs are insidious, mimicking other diseases. Misdiagnosis can result in severe adverse perinatal outcomes, even maternal/neonatal death. Early treatment with liposomal amphotericin-B (LAmB) is currently the first choice with adequate effectiveness. We report a rare case of VL in a twin pregnancy with onset at the second trimester, presenting with periodic fever with rigors, right flank pain, and gradual dysregulation of all three cell lines. The positive rK39 enzyme-linked immunosorbent assay test confirmed the diagnosis. Treatment with LAmB resulted in clinical improvement within 48 h and in the delivery of two late-preterm healthy neonates with no symptoms or signs of vertical transmission. The one-year follow-up, of the mother and the neonates, was negative for recurrence. To our knowledge, this is the first reported case of VL in a twin pregnancy, and consequently treatment and perinatal outcome are of great importance. [ABSTRACT FROM AUTHOR]

Purpose: Bupropion is an antidepressant that inhibits noradrenaline and dopamine reuptake. In the current scientific literature, there is limited information regarding the effects of bupropion on pain, predominantly derived from somatic pain studies. This study aims to investigate the impact of bupropion for the first time in visceral pain induced by colorectal distension, a pure visceral pain model, and to reveal the role of various receptors involved in pain control in this effect. Materials and Methods: Male Sprague-Dawley rats were used in the study. Visceral pain was assessed by colorectal distension-induced visceromotor response. Bupropion is administered gastrically at 5, 10, 20, and 40 mg/kg doses. The mechanism of action of bupropion at the spinal cord level was investigated by intrathecal administration of antagonists of a1 and a2 adrenoceptors (prazosin and yohimbine), D1 and D2 dopamine (SCH 23390 and sulpiride) and opioid receptors (naloxone) 10 minutes before bupropion's effective dose. Results: Bupropion showed significant antinociceptive effects at 20 and 40 mg/kg intragastric doses; no difference was found between these two doses. Intrathecally administered yohimbine (30 µg/rats), sulpiride (30 µg/rats, i. t.), and naloxone (2.5 µg/rats) diminished the antinociceptive effect of bupropion. Prazosin and SCH 23390 did not alter bupropion's effect. Conclusion: The findings show the antinociceptive effect of bupropion in visceral pain, and adrenergic, dopaminergic, and opioidergic receptors in the spinal cord play a role in this effect. [ABSTRACT FROM AUTHOR]

Study Design. A prospective, anatomical imaging study of healthy volunteer subjects in accurate surgical positions. Objective. To establish if there is a change in the position of the abdominal contents in the lateral decubitus (LD) versus prone position. Summary of background data. Lateral transpsoas lumbar interbody fusion (LLIF) in the LD position has been validated anatomically and for procedural safety, specifically in relation to visceral risks. Recently, LLIF with the patient in the prone position has been suggested as an alternative to LLIF in the LD position. Materials and Methods. Subjects underwent magnetic resonance imaging of the lumbosacral region in the right LD position with the hips flexed and the prone position with the legs extended. Anatomical measurements were performed on axial magnetic resonance images at the L4-5 disc space. Results. Thirty-four subjects were included. The distance from the skin to the lateral disc surface was 134.9 mm in prone compared with 118.7 mm in LD (P< 0.0001). The distance between the posterior aspect of the disc and the colon was 20.3 mm in the prone compared with 41.1 mm in LD (P<0.0001). The colon migrated more posteriorly in relation to the anterior margin of the psoas in the prone compared with LD (21.7 vs. 5.5 mm, respectively; P<0.0001). 100% of subjects had posterior migration of the colon in the prone compared with the LD position, as measured by the distance from the quadratum lumborum to the colon (44.4 vs. 20.5 mm, respectively; P<0.001). Conclusion. There were profound changes in the position of visceral structures between the prone and LD patient positions in relation to the LLIF approach corridor. Compared with LD LLIF, the prone position results in a longer surgical corridor with a substantially smaller working window free of the colon, as evidenced by the significant and uniform posterior migration of the colon. Surgeons should be aware of the potential for increased visceral risks when performing LLIF in the prone position. [ABSTRACT FROM AUTHOR]

Due to the low frequency and the changes in diagnostic techniques and terminology during the last few years, only little clinical information is available on splenic stromal sarcoma (SSS). This multi‐institutional study aimed at gathering clinical cases of SSS in dogs and investigates their clinical behaviour, as well as analyse possible clinicopathological prognostic factors, including the use of adjuvant therapy. Dogs with a histologically confirmed SSS that underwent splenectomy were retrospectively included. To be included in the study, either FFPE tissue blocks or multiple tissue sections had to be available for histopathologic and immunohistochemical revision. Clinical and pathological variables, along with adjuvant therapy data, were collected. Cumulative incidence of metastatic disease was analysed through univariate and bivariate analyses. The impact of adjuvant chemotherapy on metastasis incidence and survival was assessed, considering an estimated propensity score. A total of 32 dogs were included. Among them, 22 developed metastases with an incidence of 37.5%, 59.38%, and 65.94% at 6, 12, and 24 months, respectively. Univariate analysis identified mitotic count, total scoring, and necrosis as prognostic factors. In bivariate analysis, mitotic count remained prognostic. The administration of adjuvant chemotherapy did not have an impact on metastasis incidence or survival time. The study found that dogs with SSSs are at high risk of metastasis, although a small subgroup may experience longer survival after splenectomy. Mitotic count was the only variable having a reliable prognostic impact. Adjuvant chemotherapy did not appear to decrease the incidence of metastasis or prolong survival in these dogs. [ABSTRACT FROM AUTHOR]

Objective: Congenital defects/diseases. Background: Situs inversus totalis (SIT) is a rare congenital abnormality that includes mirror-image transposition of both the abdominal and the thoracic organs. It may remain undetected into adulthood until an acute medical emergency results in diagnostic imaging. This report presents a challenging case of left-sided acute appendicitis in a 45-year-old man with SIT. Case Report: A 45-year-old man with a medical history of gastroesophageal reflux disease, class 2 obesity, prediabetes, and elevated low-density lipoprotein cholesterol presented with severe acute abdominal pain localized in the left lower quadrant with localized tenderness, nausea, and 2 episodes of non-bloody and non-bilious emesis that started a day before the clinical encounter. Computed tomography of the abdomen and pelvis revealed previously undiagnosed congenital SIT. In addition, physical, laboratory, and radiological findings suggested early acute appendicitis with no evidence of complications. Hence, the patient was managed with an emergent laparoscopic appendectomy. Acute appendicitis was confirmed in the post-surgery histopathological examination. The post-surgery recovery was uneventful, and the patient was discharged home on the second postoperative day. Conclusions: This report highlights that SIT may remain undiagnosed into adulthood and poses a challenge in the diagnosis of left-side appendicitis due to atypical symptom presentation, supporting the findings of previous case reports. Therefore, the inclusion of left-sided acute appendicitis in the differential diagnosis of abdominal pain in the left lower quadrant is warranted. [ABSTRACT FROM AUTHOR]

Background: Evidence has linked low‐grade systemic inflammation and visceral adipose tissue (VAT) with development of chronic conditions. Cytokines and select proteins released by VAT may promote a low‐grade inflammatory response. A number of equations have been developed to estimate VAT levels. In this study, we compared predicted VAT equation relationships with biomarkers of inflammation. Methods: This was a cross‐sectional study of 2038 men and women aged 46–73 years. Correlation and linear regression analyses were performed to examine inflammatory biomarker relationships with four commonly assessed anthropometric measures and 10 predicted VAT equations. Results: Compared with anthropometric measures, predicted VAT equations were found to explain a greater proportion of variance in CRP (R2 =.075, p =.001), IL‐6 (R2 =.060, p =.001), TNF‐α (R2 =.017, p =.005), resistin (R2 =.011, p =.012), monocyte (R2 =.027, p =.001), eosinophil (R2 =.012, p =.01) and basophil (R2 =.015, p =.002) levels in males, and a greater variance in concentrations of C3 (R2 =.175, p =.001), IL‐6 (R2 =.090, p =.001), TNF‐α (R2 =.036, p =.001), adiponectin (R2 =.121, p =.001), the adiponectin‐to‐leptin ratio (R2 =.444, p =.001), resistin (R2 =.025, p =.001), white blood cell count (R2 =.057, p =.001), neutrophils (R2 =.061, p =.001) and lymphocytes (R2 =.020, p =.001) in females. Conclusion: Equations for assessing VAT levels might be useful to characterise metabolic health. Further studies that examine predicted VAT relationships with disease and mortality outcomes are warranted. [ABSTRACT FROM AUTHOR]

Purpose: This study aims to investigate the relationship between visceral adiposity and the possible etiologies of acute pancreatitis. Obesity creates low-grade inflammation and evidence supports an association between obesity and inflammatory conditions such as pancreatitis. CT imaging is utilized in assessing pancreatitis severity and complications but also offers the chance to quantitatively measure visceral fat area (VFA) and subcutaneous fat area (SFA). Given the metabolic role that fat plays, we hypothesized that different body fat distributions, as measured by these areas, may be associated with different etiologies. Further, this also allows us to explore a relationship between severity, etiology, and the fat distributions in patients with acute pancreatitis. Method: Retrospective observational cohort study of all patients admitted to a single center. The VFA, SFA, their ratio (VFA/SFA) and total fat area (TFA) were calculated using a semi-automatic algorithm. Results: 518 patients were admitted with acute pancreatitis over a three-year period. 177 patients underwent CT imaging. Gallstone pancreatitis patients had higher VFA and TFA measurements while alcoholic pancreatitis patients had lower measurements. Patients with pancreatitis with no clear cause had the lowest VFA/SFA ratio. Increasing VFA was associated with increasing severity in a univariate logistic regression model (p = 0.01) but this association diminished in a multivariate model accounting for etiology (p = 0.09). Conclusion: The pattern of fat distribution differs amongst the etiologies of acute pancreatitis, as this likely reflects multiple contributing pathogenic mechanisms. Patients with gallstone pancreatitis had disproportionately more visceral fat, alcohol had the least overall fat, and those without a clear cause had the lowest VFA/SFA ratio. Etiology is strongly associated with body fat distribution. Severity is associated with increased visceral fat, but much less so when etiology is controlled for. The radiological assessment of fat distribution thus can give clues to associated etiology.

Pain is a major issue in healthcare throughout the world. It remains one of the major clinical issues of our time because it is a common sequela of numerous conditions, has a tremendous impact on individual quality of life, and is one of the top drivers of cost in medicine, due to its influence on healthcare expenditures and lost productivity in those affected by it. Patients and healthcare providers remain desperate to find new, safer and more effective analgesics. Growing evidence indicates that the voltage-gated sodium channel Nav1.8 plays a critical role in transmission of pain-related signals throughout the body. For that reason, this channel appears to have strong potential to help develop novel, more selective, safer, and efficacious analgesics. However, many questions related to the physiology, function, and clinical utility of Nav1.8 remain to be answered. In this article, we discuss the latest studies evaluating the role of Nav1.8 in pain, with a particular focus on visceral pain, as well as the steps taken thus far to evaluate its potential as an analgesic target. We also review the limitations of currently available studies related to this topic, and describe the next scientific steps that have already been undertaken, or that will need to be pursued, to fully unlock the capabilities of this potential therapeutic target.

Background: Up to 30% of patients with metastatic castration-resistant prostate cancer (mCRPC) develop visceral metastases, which are associated with a poor prognosis. Objectives: Efficacy of enzalutamide in mCRPC patients with measurable metastases, including visceral and/or extra-regional lymph nodes. Methods: In this phase II multicenter study, patients with mCRPC and measurable metastases received enzalutamide as the first line. Primary endpoint: 3-month (mo) disease control rate (DCR) defined as the proportion of patients with complete (CR) or partial response (PR) or stable disease (SD) as per Response Evaluation Criteria in Solid Tumors 1.1. Secondary endpoint: safety. Exploratory endpoint: the association between ARv7 splicing variants in basal circulating tumor cell (CTC)-enriched blood samples and treatment response/resistance using the AdnaTest ProstateCancerSelect kit and the AdnaTest ProstateCancer Panel AR-V7. Results: From March 2017 to January 2021, 68 patients were enrolled. One patient never started treatment. Median age: 72 years. A total of 52 patients (78%) received enzalutamide as a first line for mCRPC. The median follow-up was 32 months. At the 3-month assessment, 24 patients presented an SD, 1 patient achieved a CR, and 23 patients had a PR (3-mo-DCR of 72%). Discontinuations due to adverse events (AEs), disease-related death, or disease progression occurred in 9%, 6%, and 48% of patients. All patients reported at least one grade (G) 1–2 AE: the most common were fatigue (49%) and hypertension (33%). Six G3 AEs were reported: two hypertension, one seizure, one fatigue, one diarrhea, and one headache. Basal detection of ARv7 was significantly associated with poor treatment response (p = 0.034) and a nonsignificant association (p = 0.15) was observed between ARv7 detection and response assessments. At month 3, ARv7 was detected in 57%, 25%, and 15% of patients undergoing progressive disease, SD, and PR, respectively. Conclusion: The study met its primary endpoint, showing the efficacy of enzalutamide in men with mCRPC and measurable metastatic lesions in visceral and/or lymph node sites. Trial registration: ClinicalTrials.gov Identifier: NCT03103724. First Posted: 6 April 2017. First patient enrollment: 19 April 2017. [ABSTRACT FROM AUTHOR]

ABSTRACT Background: Visceral leishmaniasis (VL) is a public health problem and is a relevant cause of death in developing countries. This study aimed to evaluate the 20-year survival and predictors of worse prognosis in patients with VL admitted to a reference hospital for the treatment of infectious diseases between 1995 and 2016 in northern Minas Gerais, an area of high endemicity for VL. Methods: This retrospective cohort study was conducted at a hospital in northern Minas Gerais, Brazil. All patients with VL were evaluated over a 20-year period. The medical records were thoroughly analyzed. Cox regression analysis was performed to estimate factors associated with the probability of survival. Results: The cohort included 972 individuals, mostly male children

Sexual dimorphism of visceral pain has been documented in clinics and experimental animal models. Aside from hormones, emerging evidence suggests the sex-differential intrinsic neural regulation of pain generation and maintenance. According to the International Association for the Study of Pain (IASP) and the American College of Gastroenterology (ACG), up to 25% of the population have visceral pain at any one time, and in the United States 10–15 percent of adults suffer from irritable bowel syndrome (IBS). Here we examine the preclinical and clinical evidence of sex differences in visceral pain focusing on IBS, other forms of bowel dysfunction and IBS-associated comorbidities. We summarize preclinical animal models that provide a means to investigate the underlying molecular mechanisms in the sexual dimorphism of visceral pain. Neurons and nonneuronal cells (glia and immune cells) in the peripheral and central nervous systems, and the communication of gut microbiota and neural systems all contribute to sex-dependent nociception and nociplasticity in visceral painful signal processing. Emotion is another factor in pain perception and appears to have sexual dimorphism.

BackgroundThis analysis investigated whether baseline characteristics affect the survival benefit derived from palbociclib-fulvestrant and the optimal timing of cyclin-dependent kinase 4/6 inhibitor therapy for advanced breast cancer (ABC) in patients from PALOMA-3.Patients and methodsIn total, 521 patients were randomized 2:1 to receive palbociclib (125 mg/day, 3/1 schedule)-fulvestrant (500 mg, intramuscular injection, on days 1 and 15 of cycle 1, and then day 1 of each subsequent cycle) or matching placebo-fulvestrant. Median overall survival (OS) and progression-free survival were estimated using the Kaplan-Meier method.ResultsMultivariable analysis identified endocrine sensitivity, nonvisceral disease, no prior chemotherapy for ABC, and Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 as significant prognostic factors for OS. Patients without chemotherapy for ABC had fewer prior lines of treatment in any setting and in the ABC setting versus patients with prior chemotherapy for ABC (two or fewer prior systemic therapies: 69% vs. 42%; no more than one prior line for ABC: 82% vs. 33%, respectively). Median OS was prolonged with palbociclib-fulvestrant in patients without prior chemotherapy for ABC (39.7 vs. 29.5 months; hazard ratio, 0.75; 95% confidence interval [CI]: 0.56-1.01) and was similar in patients with prior chemotherapy for ABC (25.6 vs. 26.2 months; hazard ratio, 0.91 [95% CI: 0.63-1.32]) versus placebo-fulvestrant.ConclusionPrognostic factors for OS included endocrine sensitivity, nonvisceral disease, ECOG PS of 0, and no prior chemotherapy for ABC. Exploratory analyses suggest improved OS with palbociclib-fulvestrant versus placebo-fulvestrant in patients with no prior chemotherapy for ABC, prior endocrine sensitivity, and fewer prior regimens of systemic therapy. (Clinical trial identification number: NCT01942135).Implications for practicePrognostic factors for overall survival in HR+/HER2- advanced breast cancer (ABC) include the absence of prior chemotherapy in the advanced setting, endocrine sensitivity, nonvisceral disease, and an ECOG performance status of 0. Improved overall survival benefit was observed with palbociclib-fulvestrant versus placebo-fulvestrant in patients (regardless of menopausal status or visceral involvement) with no prior chemotherapy for ABC, with prior endocrine sensitivity, and fewer prior regimens of systemic therapy. Progression-free survival was prolonged with palbociclib across subgroups (regardless of chemotherapy exposure in ABC). These exploratory findings suggest that patients may receive greater clinical benefit from palbociclib-fulvestrant if they receive the combination before chemotherapy in the advanced setting.

Cutaneous T-cell lymphoma (CTCL) is a rare hematologic malignancy that traditionally presents with cutaneous lesions, though metastases are not uncommon in progressive disease. We describe four cases of CTCL with central nervous system (CNS) involvement, detailing the history, pathological characteristics, treatment response, and progression. Median time from initial diagnosis to CNS metastasis was ∼5.4 years (range 3.4–15.5 years) and survival after metastasis was ∼160 days (range 19 days–4.4 years). No patients achieved long-term (>5 years) survival, though some displayed varying degrees of remission following CNS-directed therapy. We conclude that clinicians must be attentive to the development of CNS metastases in patients with CTCL. The growing body of literature on such cases will inform evolving therapeutic guidelines on this rare CTCL complication.

Leishmaniasis is a complex vector-borne disease caused by various Leishmania species, affecting humans and animals. Current diagnostic methods have limitations, leading to potential misdiagnosis. Therefore, there is an urgent need for specific and sensitive diagnostic tools. We evaluated the sensitivity of a quantitative real-time PCR (qPCR) assay targeting the 18S gene in diverse clinical sample matrices. The assay showed a wide dynamic range and a limit of detection (LoD) of 1 parasite equivalent per milliliter (eq-p/mL) for all tested species. It exhibited high specificity for Leishmania DNA, with no amplification against other microorganisms. When applied to samples from patients with visceral and cutaneous leishmaniasis, the qPCR assay provided results that matched the reference methods and allowed estimation of parasite burdens. This assay holds promise for diagnosing and monitoring leishmaniasis by offering high sensitivity, specificity, and the ability to estimate parasitemia. Further studies are needed to enhance Leishmania molecular diagnostics and expand their coverage for improved clinical impact.

Whilst obesity and visceral adipose tissue (VAT) have been reported to be associated with an increased risk of severe AP, the established predictive scoring systems have not yet encompassed the impact of obesity or visceral adiposity. In the acute setting, computed tomography (CT) is often performed to assess AP severity and associated complications. With the added benefit of quantifying body fat distribution, it can be opportunistically used to quantify visceral adiposity and assess its relationship with the course of AP. This systematic review identified fifteen studies evaluating the relationship between visceral adiposity measured on CT and the severity of presentations of acute pancreatitis from January 2000 to November 2022. The primary outcome was to assess the relationship between CT quantified VAT and AP severity. The secondary outcomes were to assess the impact of VAT on patients developing local and systemic complications associated with AP. Whilst ten studies showed there was a significant correlation between an increased VAT and AP severity, five studies found otherwise. The majority of current literature demonstrate a positive correlation between increased VAT and AP severity. CT quantification VAT is a promising prognostic indicator with the potential to guide initial management, prompt more aggressive treatment measures or earlier re-evaluation and to aid disease prognostication in patients with acute pancreatitis. [ABSTRACT FROM AUTHOR]

Objectives: To analyse the flow of cases of visceral leishmaniasis (VL) in the state of Ceará, Brazil, between 2007 and 2021. Methods: An ecological study was conducted using a spatial approach of newly confirmed cases of VL recorded in the Notifiable Diseases Information System. We identified individuals whose municipality of diagnosis differed from that of their residence. Flow maps, constructed using Tabwin 32 and ArcMap 9.2, allowed for the identification of the volume of traffic between the municipality of residence and that of initial care. Results: There were 6775 confirmed VL cases. As a flow indicator, 178 counties had at least one resident diagnosed in another municipality in Ceará, with 2491 VL cases and an average trip of 79 km. The largest hub for receiving cases for diagnosis was the capital Fortaleza (1478 patients from 129 other municipalities), followed by Sobral, located in the northwestern region of Ceará (599 from 55 municipalities), and Barbalha, in the southern region (171 from 29 municipalities). In this southern region, 25 municipalities moved 55 people for treatment to Juazeiro do Norte and 11 municipalities moved 39 patients to Crato. A total of 255 patients with VL from 11 municipalities in other Brazilian states, mainly from the Northeast and North, were observed and notified in health services in Ceará. Conclusions: The major centres of VL diagnosis outside residence were in the cities of Fortaleza, Sobral, Barbalha, Juazeiro do Norte and Crato. There was also an outflow of cases from other municipalities located in the northeastern and northern regions of Brazil. The flows were more intense during the first triennium of the analysis and milder from 2019 to 2021. Understanding the diagnostic flow of VL helps in decision making and the development of public policies to improve the lives of the population. [ABSTRACT FROM AUTHOR]

Leishmaniasis is a vector-borne disease caused by protozoan parasites of the genus Leishmania and is transmitted through the bite of infected female sandflies. In the Mediterranean region, visceral leishmaniasis is caused by Leishmania. infantum, and it is usually responsible for symptoms such as fever, pancytopenia and enlargement of the liver and spleen. Relapse is rare in immunocompetent patients as much as the mucous involvement. We present a rare case of mucosal relapse of visceral leishmaniasis in a child with SARS-CoV-2 infection and perform an extensive review of the literature about leishmaniasis relapses in children. Atypical mucosal involvement during Leishmaniasis relapse is an eventuality in pediatric patients. Clinical follow-up and periodic PCR tests must be considered essential for the early recognition and treatment of an eventual relapse. [ABSTRACT FROM AUTHOR]

Introduction and Objectives: Urodynamics are the accepted gold standard for the evaluation of multiple forms of voiding dysfunction. However, the tests are expensive, invasive, poorly reproducible, and often prone to artifacts. Therefore, there is a pressing need to develop next‐generation urodynamics. The purpose of this study was to develop a novel ex vivo porcine bladder urodynamics model with afferent pelvic nerve signaling that can be used as a preclinical surrogate for bladder sensation. Methods: Porcine bladders including the ureters and vascular supply were harvested from local abattoirs using an established protocol in both male and female animals. Ex vivo bladder perfusion was performed using physiologic MOPS (3‐(N‐morpholino) propanesulfonic acid) buffer solution. The pelvic nerve adjacent to the bladder was grasped with micro‐hook electrodes and electroneurogram (ENG) signals recorded at 20 kHz. Bladders were filled with saline at a nonphysiologic rate (100 mL/min) to a volume of 1 L using standard urodynamics equipment to simultaneously record intravesical pressure. ENG amplitude was calculated as the area under the curve for each minute, and ENG firing rate was calculated as number of spikes (above baseline threshold) per minute. At the conclusion of the experiment, representative nerve samples were removed and processed for nerve histology by a pathologist (hematoxylin and eosin and S100 stains). Results: A total of 10 pig bladders were used, and nerve histology confirmed the presence of nerve in all adequately processed samples. Vesical pressure, ENG firing rate, and ENG amplitude all increased as a function of filling. During filling tertiles (low fill: min 1–3, med fill: min 4–6, and high fill: min 7–10), normalized pressures were 0.22 ± 0.04, 0.38 ± 0.05, and 0.72 ± 0.07 (cmH2O). Similarly, normalized ENG firing rates were 0.08 ± 0.03, 0.31 ± 0.06, and 0.43 ± 0.04 spikes/minute, respectively, and normalized nerve amplitudes were 0.11 ± 0.06, 0.39 ± 0.06, and 0.56 ± 0.14) μV, respectively. Strong relationships between average normalized pressure values and averaged normalized ENG firing rate (r2 = 0.66) and average normalized ENG amplitude (r2 = 0.8) were identified. Conclusions: The ex vivo perfused porcine bladder can be used as a preclinical model for the development of next‐generation urodynamics technologies. Importantly, the model includes a reproducible method to measure afferent nerve activity that directly correlates with intravesical pressure during filling and could potentially be used as a surrogate measure of bladder sensation. [ABSTRACT FROM AUTHOR]

A 3-year-old dog was referred to the Veterinary Medical Teaching Hospital of the University of California-Davis for further evaluation of episodes of epistaxis of 1-year duration and peripheral lymphadenopathy. The patient had a history of atopic dermatitis with no travel history outside of California. Hyperglobulinemia with a polyclonal gammopathy was noted on serum protein electrophoresis. Microscopic evaluation of a bone marrow aspirate sample revealed many free and intra-cellular amastigotes of Leishmania sp. that was further confirmed by qPCR as L infantum. This is, to the best of our knowledge, the first reported case of canine leishmaniasis in the state of California. The patient is believed to have been vertically infected from the dam who is from Serbia and remained subclinical until presentation. Because the clinical progression of leishmaniasis is variable, it is important that precautions be discussed with owners acquiring puppies with dams from endemic regions of leishmaniasis to prevent zoonotic exposure in states where competent vectors are present.

Locally tailored interventions for neglected tropical diseases (NTDs) are becoming increasingly important for ensuring that the World Health Organization (WHO) goals for control and elimination are reached. Mathematical models, such as those developed by the NTD Modelling Consortium, are able to offer recommendations on interventions but remain constrained by the data currently available. Data collection for NTDs needs to be strengthened as better data are required to indirectly inform transmission in an area. Addressing specific data needs will improve our modelling recommendations, enabling more accurate tailoring of interventions and assessment of their progress. In this collection, we discuss the data needs for several NTDs, specifically gambiense human African trypanosomiasis, lymphatic filariasis, onchocerciasis, schistosomiasis, soil-transmitted helminths (STH), trachoma, and visceral leishmaniasis. Similarities in the data needs for these NTDs highlight the potential for integration across these diseases and where possible, a wider spectrum of diseases.

Investigation of neural circuits underlying visceral pain is hampered by the difficulty in achieving selective manipulations of individual circuit components. In this study, we adapted a dual AAV approach, used for projection-specific transgene expression in the CNS, to explore the potential for targeted delivery of transgenes to primary afferent neurons innervating visceral organs. Focusing on the extrinsic sensory innervation of the mouse colon, we first characterized the extent of dual transduction following intrathecal delivery of one AAV9 vector and intracolonic delivery of a second AAV9 vector. We found that if the two AAV9 vectors were delivered one week apart, dorsal root ganglion (DRG) neuron transduction by the second vector was greatly diminished. Following delivery of the two viruses on the same day, we observed colocalization of the transgenes in DRG neurons, indicating dual transduction. Next, we delivered intrathecally an AAV9 vector encoding the inhibitory chemogenetic actuator hM4D(Gi) in a Cre-recombinase dependent manner, and on the same day injected an AAV9 vector carrying Cre-recombinase in the colon. DRG expression of hM4D(Gi) was demonstrated at the mRNA and protein level. However, we were unable to demonstrate selective inhibition of visceral nociception following hM4D(Gi) activation. Taken together, these results establish a foundation for development of strategies for targeted transduction of primary afferent neurons for neuromodulation of peripheral neural circuits.

Metastasis to the skin remains a rare site of disease involvement in visceral malignancies. It is also a poor prognostic marker for survival. We present a case series of four cases that presented with cutaneous metastasis in a background of solid tumors of the esophagus, gall bladder, kidneys, and lungs, respectively. In all cases, the appearance of the skin lesion acted as a herald that led to the discovery of recurrence or widespread dissemination of the malignancy. Three of the patients passed away within 6 months of the appearance of skin metastases. The use of targeted therapy showed a good response in the patient with renal cell carcinoma with significant regression of disease. [ABSTRACT FROM AUTHOR]

Mike McCormack's Solar Bones entails various time-discourses which the following will trace: (I) The Temporal Trace as Form and Imprint by which the text itself leaves an iconic mark of the configuration of space into the novel's narrative time. (II) The Temporal Trace as Content and Stream through which the text accounts for the fact that it is not bound to any human notion of time. And, finally, (III) The Temporal Trace as Experience which aims at elucidating the experiential time of the reading process. Utilising Paul Ricœur's thoughts in Time and Narrative (Vol. 1–3, 1988), I will analyse and read these notions of time with and against Ricœur's integration of phenomenological time, the interplay of trace as well as the various forms of mimesis introduced in his work. Solar Bones traces multiple temporalities that make it necessary to partially reconceptualise the visceral nature of experiencing time in literary texts. [ABSTRACT FROM AUTHOR]

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Hideaki Mori,1 Tatsuya Hashimoto,1 Tetsuro Nikai,1 Motohide Furuya,2 Mai Hattori,1 Yukiko Katsube,1 Yoji Saito1 1Department of Anesthesiology, Shimane University Faculty of Medicine, Izumo, Shimane, Japan; 2Department of Psychiatry, Shimane University Faculty of Medicine, Izumo, Shimane, JapanCorrespondence: Tatsuya Hashimoto, Department of Anesthesiology, Shimane University Faculty of Medicine, 89-1 Enya-Cho, Izumo, Shimane, 693-8501, Japan, Tel +81-853-20-2295, Fax +81-853-20-2292, Email hashit@med.shimane-u.ac.jpPurpose: Remifentanil is one of the most commonly used opioids intraoperatively. Previous reports indicate that long-term use of opioids may lead to cross-tolerance to remifentanil, which poses a challenge in the control of acute pain intraoperatively. However, there is limited information regarding cross-tolerance to remifentanil, especially in visceral pain. Therefore, this study aimed to examine cross-tolerance to remifentanil in somatic and visceral tolerance using morphine-tolerant rats.Methods: Six male Sprague-Dawley rats were allocated to the morphine and saline groups each. Tolerance to the antinociceptive effect of morphine was induced in rats in the morphine group. Remifentanil was continuously infused intravenously at 10 mcg/kg/min for 120 min to assess cross-tolerance from morphine to remifentanil. The antinociceptive effects on somatic and visceral nociceptive stimuli were measured using the tail-flick (TF) and colorectal distension (CD) tests, respectively. The antinociceptive efficacy was evaluated by converting the response threshold to the percentage maximal possible effect (%MPE).Results: Remifentanil increased the %MPE in the morphine and saline groups in both the tests; however, the increase in %MPE was attenuated significantly in the morphine group compared with that in the saline group at 60, 90, and 120 min (all P < 0.01) in the TF test and at 90 and 120 min in the CD test (all P < 0.05).Conclusion: Our results indicate that morphine-tolerant rats exhibit cross-tolerance to remifentanil’s acute antinociceptive effects on somatic and visceral stimuli. Cross-tolerance to remifentanil should be considered in the perioperative management of patients using morphine.Keywords: remifentanil, morphine, cross-tolerance, somatic, visceral

Simple Summary: Hemangiosarcoma is a mesenchymal neoplasm that originates in the endothelial cells of blood vessels. According to the location of origin, they can be classified as non-visceral and visceral types. Hemangiosarcoma can be very aggressive and metastasize to distant organs. The aim of this critical review is to present data on the epidemiology, etiology, diagnosis, staging, therapeutic modalities, and prognosis of canine hemangiosarcoma based on a consensus meeting organized by the Brazilian Association of Veterinary Oncology (ABROVET) in September 2022. Recent information from the literature, as well as new results from consensus participants, are presented and discussed. Hemangiosarcoma is a mesenchymal neoplasm originating in the endothelial cells of blood vessels; they can be classified as non-visceral and visceral types. Non-visceral hemangiosarcomas can affect the skin, subcutaneous tissues, and muscle tissues; visceral hemangiosarcomas can affect the spleen, liver, heart, lungs, kidneys, oral cavity, bones, bladder, uterus, tongue, and retroperitoneum. Among domestic species, dogs are most affected by cutaneous HSA. Cutaneous HSA represents approximately 14% of all HSA diagnosed in this species and less than 5% of dermal tumors, according to North American studies. However, Brazilian epidemiological data demonstrate a higher prevalence, which may represent 27 to 80% of all canine HSAs and 13.9% of all skin neoplasms diagnosed in this species. Cutaneous HSA most commonly affects middle-aged to elderly dogs (between 8 and 15 years old), with no gender predisposition for either the actinic or non-actinic forms. The higher prevalence of cutaneous HSA in some canine breeds is related to lower protection from solar radiation, as low skin pigmentation and hair coverage lead to greater sun exposure. Actinic changes, such as solar dermatosis, are frequent in these patients, confirming the influence of solar radiation on the development of this neoplasm. There are multiple clinical manifestations of hemangiosarcoma in canines. The diagnostic approach and staging classification of cutaneous HSAs are similar between the different subtypes. The definitive diagnosis is obtained through histopathological analysis of incisional or excisional biopsies. Cytology can be used as a presurgical screening test; however, it has little diagnostic utility in cases of HSA because there is a high risk of blood contamination and sample hemodilution. Surgery is generally the treatment of choice for dogs with localized non-visceral HSA without evidence of metastatic disease. Recently, electrochemotherapy (ECT) has emerged as an alternative therapy for the local ablative treatment of different neoplastic types; the use of radiotherapy for the treatment of dogs with cutaneous HSA is uncommon. There is greater consensus in the literature regarding the indications for adjuvant chemotherapy in subcutaneous and muscular HSA; doxorubicin is the most frequently used antineoplastic agent for subcutaneous and muscular subtypes and can be administered alone or in combination with other drugs. Other therapies include antiangiogenic therapy, photodynamic therapy, the association of chemotherapy with the metronomic dose, targeted therapies, and natural products. The benefits of these therapies are presented and discussed. In general, the prognosis of splenic and cardiac HSA is unfavorable. As a challenging neoplasm, studies of new protocols and treatment modalities are necessary to control this aggressive disease. [ABSTRACT FROM AUTHOR]

Visceral leishmaniasis is a form of parasitic infection transmitted to human beings by the bites of female sandflies of the genus Phlebotomus in African countries, including Nigeria. This study was carried out in Ekemkpon community of Cross River State in Southern Nigeria, as a survey for the presence of leishmanial antibodies in the area. Four millilitres of blood specimens were collected, by venepuncture, from 178 consenting residents of the study community. One millilitre of cellfree serum from each blood specimen was placed in a plain test tube, to which 2 drops of concentrated formalin (40%) were added. The preparation was allowed to stand on the bench for 20 minutes. A positive Formol Gel test was indicated by the whitening and gelling of the serum like the white of an egg within 5 minutes, Chi-Square technique was used for testing the statistical significance of all parameters during analysis. A total of 178 residents, comprising 95 males and 83 females, were enlisted in the study after obtaining their oral consent. Positive formol gel results were detected in 24 subjects. This finding gave an overall prevalence of 13.5% (24:178) for visceral leishmaniasis in the study area. Among the residents of the study area, there were no skin manifestations suggestive of cutaneous forms of leishmaniasis. Among those who were positive for the formol gel test, there were no overt signs of classical illness. Therefore, visceral leishmaniasis exists as an asymptomatic infection in this community. It is recommended that more sensitive tests, especially molecular techniques, be carried out for a definitive diagnosis to establish the presence or absence of visceral leishmaniasis in this community. [ABSTRACT FROM AUTHOR]

An approximately 12‐year‐old female Vietnamese Pot‐Bellied Pig was presented to the Mississippi State College of Veterinary Medicine Food Animal Service for anorexia of 2 days duration. On physical examination, the patient appeared depressed and lethargic with significantly pale mucus membranes, open mouth breathing, and nostril flaring. On abdominal palpation, the abdomen was tense and uncomfortable. A complete blood count (CBC) and chemistry profile were performed. The CBC revealed significant anemia and mild leukocytosis characterized by mild neutrophilia with a left shift. Mast cells were rarely observed. Hematocrit = 8.1% (RI 22‐50), RBC = 1.25 × 106/μL (RI 3.6‐7.8), WBC = 19.85 × 103/μL (RI 5.2‐17.9), Neutrophils = 15.08 × 103/μL (RI 0‐11.4), and Bands = 0.993 × 103/μL (RI 0‐0.019). The chemistry profile was unremarkable with a mildly elevated BUN and slightly decreased total protein and albumin (BUN = 39 mg/dL [RI 4.2‐15.1], total protein = 6.2 g/dL [RI 6.6‐8.9], and albumin = 2.5 g/dL [RI 3.6‐5.0]). An abdominal ultrasound revealed numerous hypoechoic nodules diffusely scattered throughout the hepatic parenchyma. An FNA of one of the hepatic nodules was performed. A mild suppurative component and numerous variably granulated mast cells were observed. A presumptive cytologic diagnosis of mast cell tumor was made. Histopathology was performed, confirming the cytologic interpretation. [ABSTRACT FROM AUTHOR]

Leishmaniasis, one of the most neglected tropical diseases (NTDs), is the third most important vector-borne disease worldwide. This disease has a global impact and severity of the infection and is greatest in the Middle East. The agent of infection is a protozoan parasite of the genus, Leishmania, and is generally transmitted by blood-sucking female sandflies. In humans, there are three clinical forms of infection: (1) cutaneous (CL), (2) mucocutaneous (ML), and (3) visceral leishmaniasis (VL). This review aims to discuss the current epidemiological status of leishmaniasis in Saudi Arabia, Iraq, Syria, and Yemen with a consideration of treatment options. The elevated risk of leishmaniasis is influenced by the transmission of the disease across endemic countries into neighboring non-infected regions. [ABSTRACT FROM AUTHOR]