Precision medicine involves tailoring an individual’s genes or proteins to prevent, diagnose, or treat diseases such as cancer. Given the recent advances in cancer immunotherapy, there is now a focus on developing vaccines as a new treatment modality. Therapeutic vaccines for cancer are a precision medicine approach that has made enormous progress in recent years due to advances in vaccine engineering. This technology uses antigens derived from the patient’s tumor to create vaccines that are unique and specific to that patient. Although challenges remain, significant progress has been made in recent years, largely due to the advent of mRNA vaccines. This mini-review primarily focuses on developments in vaccine engineering, outstanding therapeutic obstacles, and recent human clinical trials.

The treatment of Helicobacter pylori (H. pylori) infection remains a challenge due to the increasing prevalence of drug-resistant bacteria. It is hypothesized that using more potent acid suppressants, such as potassium-competitive acid blockers (P-CABs) like Vonoprazan, may improve eradication rates. The aim of this study was to compare the effectiveness of H. pylori eradication regimens containing Vonoprazan with those containing proton pump inhibitors for H. pylori infection.

Two hundred and thirty-two patients were assigned to two groups. Group I (treatment-naïve) included: Arm 1 (intervention arm) with 58 patients who received Clarithromycin 500 mg twice daily, Amoxicillin 1 mg twice daily, and Vonoprazan 20 mg twice daily; and Arm 2 (comparator arm) with 58 patients who received Clarithromycin 500 mg twice daily, Amoxicillin 1 mg twice daily, and Esomeprazole 20 mg twice daily. Group II (treatment-experienced) included: Arm 3 (intervention arm) with 58 patients who received Levofloxacin 500 mg once daily, Vonoprazan 20 mg twice daily, Nitazoxanide 500 mg twice daily, and Doxycycline 100 mg once daily; and Arm 4 (comparator) with 58 patients who received Levofloxacin 500 mg once daily, Esomeprazole 20 mg twice daily, Nitazoxanide 500 mg twice daily, and Doxycycline 100 mg once daily. All patients received their treatment regimens for 14 days. H. pylori eradication was assessed four weeks after treatment.

The successful eradication rate was higher in Arm 1 (58.6%) compared to Arm 2 (50%), and higher in Arm 3 (50%) compared to Arm 4 (43.1%). H. pylori eradication regimens including P-CABs were well-tolerated with a low incidence of adverse events.

The results of P-CAB-based eradication regimens are comparable to those of proton pump inhibitor-based regimens.

Disorders of blood lipids and lipoproteins are a global problem and a high-risk factor for atherosclerosis in patients with rheumatoid arthritis (RA). This article presents data on the influence of inflammation on proatherogenic disorders of lipid and lipoprotein metabolism, with an emphasis on proinflammatory cytokines. It analyzes the blood lipid profile in RA patients and identifies the need to study subfractions of high-density lipoproteins and their function in reverse cholesterol transport in RA patients as a more promising direction for clarifying cardiovascular risk. Depending on their type and metabolites, lipids may either promote disease progression or protect against RA. Supported by the close connection between altered lipid metabolism and chronic autoimmune inflammation, specific lipid profiles are emerging as unique disease biomarkers with diagnostic, predictive, and prognostic potential. Studying the influence of the immunoinflammatory process on lipids and lipoproteins in the blood of patients with RA will not only deepen knowledge about the pathogenesis of chronic inflammation but also expand understanding of the pathogenetic and prognostic significance of lipids, allowing for early diagnosis of dyslipidemia in RA at a qualitatively new level.

Inflammatory Bowel Diseases (IBD) still represent a significant medical challenge. The course of IBD is characterized by the development of fibrotic, inflammatory, or dysplastic lesions over time. Recent advancements in operative endoscopy have introduced new strategies to address these issues. Inflammatory and fibrotic strictures pose a challenge for clinicians and represent a surgical risk. Endoscopic treatments include dilation, stent placement, and electroincisional techniques. Moreover, endoscopic approaches can also be considered in the management of IBD-related surgical complications. Addressing colorectal dysplastic lesions is a crucial concern, and several resection endoscopic techniques are available, including endoscopic mucosal resection and endoscopic submucosal dissection. This review aimed to summarize the pros and cons of advanced therapeutic endoscopic approaches in the management of IBD.

Based on our experimental and clinical research, the gastroschisis is formed by raised intraluminal and intraabdominal pressure in combination with potential weak points. The psycho-neuro-endocrine-target organ axis of young mothers, who themselves struggle to meet their macro and micronutrient requirements, places a burden on the placenta. The associated smoking, alcohol, drugs, and other toxins, leads to fetal distress. This activates the same fetal axis, with the final common pathway being activated via the sacral parasympathetic nervous system as a flight or fight response leading to colorectal secreto-motility disorder of the hindgut and small left colon leading to partial functional obstruction of hindgut. This leads to pressure build-up on the proximal colon. An intact ileocecal valve leads to blind loop obstruction, creating the force required to herniate the bowel through the defect at three key points of weakness in the abdominal wall, the most vulnerable being the right paraumbilical region. If the ileocecal valve becomes incompetent, variants of gastroschisis may occur. The fetus, particularly the peritoneum, always has a tendency to heal defects quickly, which forms secondary events in the eviscerated bowel causing the closing and closed gastroschisis with vanishing organs. Recent technological advances in preformed silastic silo innovation, prenatal diagnosis and monitoring for closing gastroschisis, perinatal management, percutaneous central long lines, and innovative minimally invasive bedside procedures, have all made significant contributions. We believe that gastroschisis is the external surgical symptom and peak of the iceberg, secondary to an underlying colorectal motility disorder, providing the force to eviscerate bowel loops through potential weak points and its subsequent sequelae.

Feedback loops or compensatory mechanisms are present in a wide range of biological systems and processes. Here, we hypothesize that endogenous opioid peptides, such as endorphins and enkephalins, can be broken down and enzymatically converted to catecholamines (dopamine, norepinephrine, epinephrine) locally. Particularly, this proposed local production of norepinephrine may modulate analgesia through feedback mechanisms. A similar arrangement may occur for corticotropin-releasing factor and adrenocorticotropic hormone (hypothalamic-pituitary-adrenal axis mediation), insulin (blood glucose regulation), and angiotensin II (cardiovascular regulation). Endorphins, enkephalins, and dynorphins have an initial amino acid sequence of Tyr-Gly-Gly-Phe, where tyrosine (and possibly phenylalanine) could be enzymatically clipped from the peptide and converted to catecholamines locally, through the canonical biosynthetic molecular pathway for catecholamines. Spatially and possibly temporally precise conversion of these terminal amino acids to catecholamines may allow them to be produced “on demand” in specific regions of the brain, spinal cord, or periphery. This hypothesis is readily testable by infusing stable isotopically labeled opioids into the brain or periphery of model organisms, and observing through liquid chromatography-mass spectrometry whether the terminal amino acids of these opioids are converted to catecholamines.

Like other drugs, adjuvants are ligands with distinct structures that interact with specific cell receptors, modulating the immune response. This definition excludes formulations and delivery systems. New adjuvants may be discovered using methods based on a ligand and its receptor’s structural and functional traits, a process known as rational drug design. This strategy requires detailed information about both the receptors and their ligands. Such information is obtained using techniques like X-ray crystallography and 2D-nuclear magnetic resonance (NMR) to establish the spatial interactions between a ligand’s functional groups and its receptor. This data is necessary to establish reliable structure-activity relationships, which, when applied to computer-aided drug design, facilitate the creation of better adjuvants as an empirical strategy. Since Quillaja saponin adjuvants likely act separately on innate and adaptive immune cells via specific functional groups and unidentified cell receptors, it is crucial to identify these receptors. This task may be achieved using bioorthogonal chemistry and proteomic methods to identify and isolate the receptors. Initially focusing on those unidentified receptors where chemical modifications of these glycosides, such as the aldehyde group and fucose residue, cause drastic changes in adjuvanticity. The isolated receptor(s) can then be characterized by X-ray crystallography and/or 2D-NMR; this information can be applied to computer-aided drug design to rationally design new derivatives. This methodology will prevent the proposition of dubious structure-activity relationships based on incomplete immunological data, unknown receptors, and unsuspected physical factors, providing essential information for designing new adjuvants and elucidating these compounds’ mechanisms of action.

With the increasing use of artificial intelligence (AI) in diagnostics, AI algorithms have shown great potential in aiding diagnostics. As more of these algorithms are developed, there is overwhelming enthusiasm for implementing digital and artificial intelligence-based pathology (DAIP), but doubts and pitfalls are also emerging. However, few original or review articles address the limitations and practical aspects of implementing DAIP. In this review, we briefly examine the evidence related to the benefits and pitfalls of DAIP implementation and argue that DAIP is not suitable for every clinical laboratory.

We searched the PubMed database using the following keywords: “digital pathology,” “digital AI pathology,” and “AI pathology.”. Additionally, we incorporated personal experiences and manually searched related papers.

Ninety-two publications were found, of which 24 met the inclusion criteria. Many advantages of DAIP were discussed, including improved diagnostic accuracy and equity. However, several limitations of implementing DAIP exist, such as financial constraints, technical challenges, and legal/ethical concerns.

We found a generally favorable but cautious outlook for the implementation of DAIP in the pathology workflow. Many studies have reported promising outcomes in using AI for diagnosis and analysis; however, there are also several noteworthy limitations in implementing DAIP. Therefore, a balance between the benefits and pitfalls of DAIP must be thoroughly articulated and examined in light of the institution’s needs and goals before making the decision to implement DAIP. Approaches for mitigating machine learning biases were also proposed, and the adaptation and growth of the pathology profession were discussed in light of DAIP development and advances.

Alpha-1 antitrypsin deficiency (AATD) is a genetic disorder associated with liver disease, ranging from fibrosis to hepatocellular carcinoma. The disease remains asymptomatic until its final stages when liver transplantation is the only available therapy. Biomarkers offer an advantage for disease evaluation. The presence of microRNAs (miRNAs) in plasma extracellular vesicles (EVs) presents a noninvasive approach to assess the molecular signatures of the disease. In this study, we aimed to identify miRNA biomarkers to distinguish molecular signatures of the liver disease associated with AATD in AATD individuals.

Using small RNA sequencing and qPCR, we examined plasma EV miRNAs in healthy controls (n = 20) and AATD patients (n = 17). We compared the EV miRNAs of AATD individuals with and without liver disease, developing an approach for detecting liver disease. A set of miRNAs identified in the AATD testing cohort was validated in a separate cohort of AATD patients (n = 45).

We identified differential expression of 178 EV miRNAs in the plasma of the AATD testing cohort compared to controls. We categorized AATD individuals into those with and without liver disease, identifying 39 differentially expressed miRNAs. Six miRNAs were selected to test their ability to discriminate liver disease in AATD. These were validated for their specificity and sensitivity in an independent cohort of 45 AATD individuals. Our logistic model established composite scores with three- and four-miRNA combinations, achieving areas under the curve of 0.737 and 0.751, respectively, for predicting AATD liver disease.

We introduce plasma EV-derived miRNAs as potential biomarkers for evaluating AATD liver disease. Plasma EV-associated miRNAs may represent a molecular signature of AATD liver disease and could serve as valuable tools for its detection and monitoring.

Human papillomavirus (HPV)-related oropharyngeal cancers associated with sexual contact are increasing, with high rates in men who have sex with men. HPV-related cancers have the advantage of being frequently detectable through oropharyngeal visual examination and having much higher survival rates than classic oropharyngeal cancers. It has been demonstrated that gay and bisexual men can take smartphone oropharyngeal “selfies” of sufficient quality for screening. However, there is an issue with the inability to move the tongue to allow a clear view of the palatine tonsils, where a majority of oropharyngeal cancer cases occur. We attempted to investigate the feasibility of using commercially available videoscopes to visualize the oropharynx. Fourteen healthy volunteers used a provided low-cost commercial endoscope to video their oropharynx. Participants used the videoscope connected to a laptop and could visualize the oropharynx on the screen. Attempts were observed, and the process was noted. A focus group of participants was carried out immediately afterwards to ascertain barriers and facilitators to using the videoscopes. All participants were able to use the videoscope and obtain videos of sufficient clarity to note major oropharyngeal landmarks. The palatine tonsils were initially difficult to visualize because the tongue could not be sufficiently controlled. Participants were given time to practice using visual cues to control the position of the tongue, which helped in obtaining good videos. Videoscopes can be used effectively with minimal instruction and provide a better view than still images, as they illuminate and magnify the site. Low-cost commercially available videoscopes may be an improvement over smartphone “selfies”.