Deep learning assisted COVID-19 detection using full CT-scans.

The ongoing pandemic of COVID-19 has shown the limitations of our current medical institutions. There is a need for research in automated diagnosis for speeding up the process while maintaining accuracy and reducing the computational requirements. This work proposes an automated diagnosis of COVID-19 infection from CT scans of the patients using deep learning technique. The proposed model, ReCOV-101, uses full chest CT scans to detect varying degrees of COVID-19 infection. To improve the detection accuracy, the CT-scans were preprocessed by employing segmentation and interpolation. The proposed scheme is based on the residual network that takes advantage of skip connection, allowing the model to go deeper. The model was trained on a single enterprise-level GPU. It can easily be provided on a network's edge, reducing communication with the cloud, often required for larger neural networks. This work aims to demonstrate a less hardware-intensive approach for COVID-19 detection with excellent performance that can be combined with medical equipment and help ease the examination procedure. With the proposed model, an accuracy of 94.9% was achieved.

Centrin-Deleted Leishmania donovani Parasites Help CD4+ T Cells to Acquire Th1 Phenotype and Multi-Functionality Through Downregulation of CD200-CD200R Immune Inhibitory Axis.

The protozoan parasite Leishmania has evolved several strategies to undermine host defense mechanisms by inducing Th2-type adaptive immunity and suppressing effector functions of Th1 phenotype. In our earlier studies, using centrin gene-deleted Leishmania (LdCen-/-) parasites as an immunogen, we have shown induction of an effective Th1-type immunity and robust memory responses that mediate protection against virulent challenge. However, role of inhibitory signals in Leishmania vaccine induced immunity in general, and LdCen-/- in particular has not been studied. Herein, we report that immunization with LdCen-/- parasites produces more functional Th1-type CD4+ T cells via downregulation of CD200-CD200R immune inhibitory axis compared to wild-type infection. We found that expression of CD200 and CD200R was significantly reduced in LdCen-/- infection compared to wild-type infection. Diminished CD200-CD200R signaling in LdCen-/- infection enabled proliferation of CD4+ T cells and resulted in the induction of pro-inflammatory cytokines and suppression of anti-inflammatory response. The effects of diminished CD200-CD200R signaling by LdCen-/- were most evident in the suppression of IL-10-producing CD4+ T cells that helped enhance more Th1 cytokine producing and multi-functional T cells compared to wild-type infection. In vivo blocking of CD200 expression with anti-CD200 treatment in wild-type infected mice limited Th2 response as indicated by reduction of IL-10-producing Tr1 cells and reduced parasite burden. On the other hand, treatment with anti-CD200 improved the LdCen-/- vaccine-induced multifunctional response and reduction in splenic parasite load upon challenge. Taken together, these studies demonstrate the role of CD200-CD200R signals in the protection induced by LdCen-/- parasites.

Whole genome sequencing of live attenuated Leishmania donovani parasites reveals novel biomarkers of attenuation and enables product characterization.

No licensed human vaccines are currently available against leishmaniasis. Several anti-leishmanial vaccines are currently undergoing testing, including genetically modified live-attenuated parasite vaccines. Studies with live attenuated Leishmania vaccines such as centrin deleted Leishmania donovani parasites (LdCen -/-) showed protective immunity in animal models. Such studies typically examined the biomarkers of protective immunity however the biomarkers of attenuation in the parasite preparations have not received adequate attention. As several candidate vaccines enter clinical trials, a more complete product characterization to enable maintenance of product quality will help meet regulatory requirements. Towards this goal, we have determined the complete genome sequence of LdCen -/- and its parent strain Ld1S-2D (LdWT) and characterized the LdCen -/- vaccine strain using bioinformatics tools. Results showed that the LdCen -/- parasites, in addition to loss of the centrin gene, have additional deletions ranging from 350 bp to 6900 bp in non-contiguous loci on several chromosomes, most commonly in untranslated regions. We have experimentally verified a subset of these adventitious deletions that had no impact on the attenuation of the LdCen -/- parasites. Our results identified hitherto unknown features of attenuation of virulence that could be used as markers of product quality in production lots and highlight the importance of product characterization in parasitic vaccines.

Immunization with Live Attenuated Leishmania donovani Centrin-/- Parasites Is Efficacious in Asymptomatic Infection.

Currently, there is no vaccine against visceral leishmaniasis (VL). Toward developing an effective vaccine, we have reported extensively on the immunogenicity of live attenuated LdCentrin-/- mutants in naive animal models. In VL endemic areas, asymptomatic carriers outnumber symptomatic cases of VL and are considered to be a reservoir of infection. Vaccination of asymptomatic cases represents a viable strategy to eliminate VL. Immunological correlates of protection thus derived might have limited applicability in conditions where the immunized host has prior exposure to virulent infection. To examine whether LdCen-/- parasites can induce protective immunity in experimental hosts that have low-level parasitemia from a previous exposure mimicking an asymptomatic condition, we infected C57Bl/6 mice with wild-type Leishmania donovani parasites expressing LLO epitope (LdWT LLO 103, i.v.). After 3 weeks, the mice with low levels of parasitemia were immunized with LdCen-/- parasites expressing 2W epitope (LdCen-/-2W 3 × 106 i.v.) to characterize the immune responses in the same host. Antigen experienced CD4+ T cells from the asymptomatic (LdWT LLO infected) LdCen-/-2W immunized, and other control groups were enriched using LLO- and 2W-specific tetramers, followed by Flow cytometric analysis. Our analysis showed that comparable CD4+ T cell proliferation and CD4+ memory T cell responses (TCM) represented by CD62Lhi, CCR7+, and IL-7R+ T cell populations were induced with LdCen-/-2W in both asymptomatic and naive animals that received LdCen-/- immunization. Upon restimulation with peptide, TCM cells differentiated into effector T cells and there was no significant difference in the recall response in animals with asymptomatic infection. Following virulent challenge, comparable reduction in splenic parasite burden was observed in both asymptomatic and naive LdCen-/- immunized animals concomitant with the development of multifunctional CD4+ and CD8+ T cells. Further, LdCen-/-2W immunization resulted in complete clearance of the preexisting asymptomatic infection (LdWT LLO ). Our results demonstrate that LdCen-/-2W immunization could be efficacious for use in asymptomatic VL individuals. Further, immunization with LdCen-/- could help in reducing the parasite burden in the asymptomatic cases and aid in controlling the VL in endemic areas.

Modulation of Innate Immune Mechanisms to Enhance Leishmania Vaccine-Induced Immunity: Role of Coinhibitory Molecules.

No licensed human vaccines are currently available against any parasitic disease including leishmaniasis. Several antileishmanial vaccine formulations have been tested in various animal models, including genetically modified live-attenuated parasite vaccines. Experimental infection studies have shown that Leishmania parasites utilize a broad range of strategies to undermine effector properties of host phagocytic cells, i.e., dendritic cells (DCs) and macrophages (MΦ). Furthermore, Leishmania parasites have evolved strategies to actively inhibit TH1 polarizing functions of DCs and to condition the infected MΦ toward anti-inflammatory/alternative/M2 phenotype. The altered phenotype of phagocytic cells is characterized by decreased production of antimicrobial reactive oxygen, nitrogen molecules, and pro-inflammatory cytokines, such as IFN-γ, IL-12, and TNF-α. These early events limit the activation of TH1-effector cells and set the stage for pathogenesis. Furthermore, this early control of innate immunity by the virulent parasites results in substantial alteration in the adaptive immunity characterized by reduced proliferation of CD4(+) and CD8(+) T cells and TH2-biased immunity that results in production of anti-inflammatory cytokines, such as TGF-ß, and IL-10. More recent studies have also documented the induction of coinhibitory ligands, such as CTLA-4, PD-L1, CD200, and Tim-3, that induce exhaustion and/or non-proliferation in antigen-experienced T cells. Most of these studies focus on viral infections in chronic phase, thus limiting the direct application of these results to parasitic infections and much less to parasitic vaccines. However, these studies suggest that vaccine-induced protective immunity can be modulated using strategies that enhance the costimulation that might reduce the threshold necessary for T cell activation and conversely by strategies that reduce or block inhibitory molecules, such as PD-L1 and CD200. In this review, we will focus on the polarization of antigen-presenting cells and subsequent role of costimulatory and coinhibitory molecules in mediating vaccine-induced immunity using live-attenuated Leishmania parasites as specific examples.

Multipurpose internal retractor for Single-incision surgery (SIS): single-institution case series.

Single-incision laparoscopic surgery (SIS) is less invasive than standard laparoscopic surgery; however, it is more difficult due to restriction of motion and the impossibility to use assistants. To overcome these obstacles, we developed a self-sustaining multipurpose internal retractor by attaching a Lone Star retractor hook to a laparoscopic bulldog clamp. Herein, we report our SIS experience using our novel retractor. Between October 2008 and April 2011, 104 patients underwent SIS using the internal retractor: 67 bandings (43% simultaneous hiatal hernia repair), 8 sleeve gastrectomies, 27 cholecystectomies, and 2 Nissen fundoplication. Mean age was 40 (range, 21 to 85) and mean body mass index was 40 kg/m (range, 20 to 64 kg/m). No intraoperative complications were observed from the use of the retractor but 2 cases required additional retraction due to liver size. This retractor has been successfully used for different SIS procedures showing to be safe, adaptable, and easy to use, lessening some challenges of SIS.

Laparoscopic aneurysm resection and splenectomy for splenic artery aneurysm in the third trimester of pregnancy.

BACKGROUND: Splenic artery aneurysms (SAA) are a rare entity most commonly diagnosed incidentally. Their association with pregnancy increases the risk of rupture resulting in a disproportionately high maternal and fetal mortality. Accordingly, elective surgical treatment is recommended in asymptomatic patients with aneurysms less than 2 cm. In this case, we present a patient during her third trimester of pregnancy with a SAA who was treated by laparoscopic aneurysm resection and splenectomy. METHODS: The patient is a 38-year-old multiparous woman, with an incidental diagnosis of a SAA in 2010. Subsequently, the patient became pregnant and at 27 weeks started to develop abdominal pain. Failed embolization was attempted with worsening of the patient's symptoms. A CT angiogram revealed a 1.6 cm distal third SAA without any evidence of rupture. Due to the localization of the lesion, the patient was offered a laparoscopic aneurysm resection and splenectomy. RESULTS: Operating time was 90 min and estimated blood loss was 5 cc. Postoperative fetal monitoring was normal. No perioperative complications were observed. The patient was discharged on postoperative day 3. Two months after laparoscopic splenectomy, the patient delivered a male infant in perfect health. CONCLUSIONS: Although this is a rare disease, the risk of aneurysmal rupture is increased during pregnancy. As a result of high maternal and fetal mortality, elective surgery should be performed. Laparoscopic surgery is the technique of choice.

Single-incision robotic-assisted living donor nephrectomy: case report and description of surgical technique.

The introduction of laparoscopic surgery, and more recently of robotics, has increased the number of living donor kidney transplants. This approach has already improved living donor acceptance rates. Even newer developments in the field have now been introduced with the purpose of further reducing postoperative pain and length of hospital stay, while offering better cosmetic results. In particular, single-incision surgery has gained popularity by improving the well-known benefits of minimally invasive surgery. In this case report, we present the first single-incision robotic-assisted living donor nephrectomy.

Serum anti-glycan antibody biomarkers for inflammatory bowel disease diagnosis and progression: a systematic review and meta-analysis.

BACKGROUND: Anti-glycan antibody serologic markers may serve as a useful adjunct in the diagnosis/prognosis of inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC). This meta-analysis/systemic review aimed to evaluate the diagnostic value, as well as the association of anti-glycan biomarkers with IBD susceptible gene variants, disease complications, and the need for surgery in IBD. METHODS: The diagnostic odds ratio (DOR), 95% confidence interval (CI), and sensitivity/specificity were used to compare the diagnostic value of individual and combinations of anti-glycan markers and their association with disease course (complication and/or need for surgery). RESULTS: Fourteen studies were included in the systemic review and nine in the meta-analysis. Individually, anti-Saccharomyces cervisiae antibodies (ASCA) had the highest DOR for differentiating IBD from healthy (DOR 21.1; 1.8-247.3; two studies), and CD from UC (DOR 10.2; CI 7.7-13.7; seven studies). For combination of ≥2 markers, the DOR was 2.8 (CI 2.2-3.6; two studies) for CD-related surgery, higher than any individual marker, while the DOR for differentiating CD from UC was 10.2 (CI 5.6-18.5; three studies) and for complication was 2.8 (CI 2.2-3.7; two studies), similar to individual markers. CONCLUSIONS: ASCA had the highest diagnostic value among individual anti-glycan markers. While anti-chitobioside carbohydrate antibody (ACCA) had the highest association with complications, ASCA and ACCA associated equally with the need for surgery. Although in most individual studies the combination of ≥2 markers had a better diagnostic value as well as higher association with complications and need for surgery, we found the combination performing slightly better than any individual marker in our meta-analysis.

Staple versus fibrin glue fixation in laparoscopic total extraperitoneal repair of inguinal hernia: a systematic review and meta-analysis.

BACKGROUND: Fixation of mesh is typically performed to minimize risk of recurrence in laparoscopic inguinal hernia repair. Mesh fixation with staples has been implicated as a cause of chronic inguinal pain. Our study aim is to compare mesh fixation using a fibrin sealant versus staple fixation in laparoscopic inguinal hernia and compare outcomes for hernia recurrence and chronic inguinal pain. METHODS AND PROCEDURES: PubMed was searched through December 2010 by use of specific search terms. Inclusion criteria were laparoscopic total extraperitoneal repair inguinal hernia repair, and comparison of both mesh fibrin glue fixation and mesh staple fixation. Primary outcomes were inguinal hernia recurrence and chronic inguinal pain. Secondary outcomes were operative time, seroma formation, hospital stay, and time to return to normal activity. Pooled odds ratios (OR) were calculated assuming random-effects models. RESULTS: Four studies were included in the review. A total of 662 repairs were included, of which 394 were mesh fixed by staples or tacks, versus 268 with mesh fixed by fibrin glue. There was no difference in inguinal hernia recurrence with fixation of mesh by staples/tacks versus fibrin glue [OR 2.13; 95% confidence interval (CI) 0.60-7.63]. Chronic inguinal pain (at 3 months) incidence was significantly higher with staple/tack fixation (OR 3.25; 95% CI 1.62-6.49). There was no significant difference in operative time, seroma formation, hospital stay, or time to return to normal activities. CONCLUSIONS: The meta-analysis does not show an advantage of staple fixation of mesh over fibrin glue fixation in laparoscopic total extraperitoneal inguinal hernia repair. Because fibrin glue mesh fixation with laparoscopic inguinal hernia repair achieves similar hernia recurrence rates compared with staple/tack fixation, but decreased incidence of chronic inguinal pain, it may be the preferred technique.