Diagnostics, Volume 13, Issue 18 (September-2 2023) – 159 articles

Cryptorchidism (CO) is a risk factor for the development of testicular germ-cell tumors (TGCT). This is supported by reports showing the persistence of gonocytes in CO patients. These cells are proposed to be related to the development of germ-cell neoplasia in situ (GCNIS), which is considered the precursor stage/lesion of TGCT. Therefore, it is proposed that some patients with CO could express some molecular markers related to TGCT. In this study, we analyzed testicular tissue samples from CO, TGCT, and controls. We determined the expression of POU5F1, PLAP, and KIT by immunohistochemistry and that of the hsa-miR-371-373 cluster, hsa-miR-367, and LATS2, PTEN, and IGFR1 genes by RT-qPCR. We then carried out a bioinformatic analysis to identify other possible candidate genes as tumor biomarkers. We found that 16.7% (2/12) of the CO patients presented increased expression of POU5F1, KIT, PLAP, hsa-miR-371-373, and hsa-miR-367 and decreased expression of LATS2 and IGF1R. Finally, the genes ARID4B, GALNT3, and KPNA6 were identified as other possible candidate tumor biomarkers. This is the first report describing the expression of the hsa-miR-371-373 cluster, hsa-miR-367, LATS2, and IGF1R in the testicular tissues of two CO patients with cells immune-positive to POU5F1, PLAP, and KIT, which is similar to what is observed in TGCT. Full article

Heparin-induced thrombocytopenia (HIT) is a life-threatening complication of heparin therapy (both unfractionated heparin and low-molecular-weight heparin). In our study, we examined a group of 122 patients with suspected HIT. The samples of all patients were analyzed in the first step using an immunoassay (ID-PaGIA Heparin/PF4, Hemos1L-Acustar HIT IgG, ZYMUTEST HIA Monostrip IgG) to detect the presence of antibodies against heparin–PF4 complexes (platelet factor 4). When the immunoassay was positive, the sample was subsequently analyzed for HIT with a functional flow cytometry assay, the HITAlert kit, the purpose of which was to demonstrate the ability of the antibodies present to activate platelets. A diagnosis of HIT can be made only after a positive functional test result. In this article, we present an overview of our practical experience with the use of the new functional method of analysis, HIT, with flow cytometry. In this work, we compared the mutual sensitivity of two functional tests, SRA and the flow cytometry HITAlert kit, in patients perceived as being at risk for HIT. This work aims to delineate the principle, procedure, advantages, pitfalls, and possibilities of the application of the functional test HITAlert using flow cytometry. Full article

Background: The present study was designed to assess the feasibility and reliability of a Continuous Glucose Monitoring System (CGMS) in a population of asphyxiated neonates during therapeutic hypothermia. Methods: This non-randomized feasibility study was conducted in the Neonatal Intensive Care Unit (NICU) facilities of Fondazione Policlinico A. Gemelli IRCSS. Infants matching the criteria for hypothermic treatment were included in this study and were connected to the CGMS (Medtronic, Northridge, CA, USA) within the first 12 h of life. Hypoglycemia was defined as a glucose value ≤ 47 mg/dL, and hyperglycemia was defined as a glucose value ≥ 180 mg/dL. Data obtained via the CGMS were compared with those obtained via a point-of-care blood glucometer (GTX). Results: The two measuring techniques were compared using the Modified Clarke Error Grid (MCEG). Sixteen infants were enrolled. The sensor had an average (standard deviation) duration of 93 (38) h. We collected 119 pairs of glycemia values (CGMVs) from the CGMS vs. GTX measurements. The CGMS detected twenty-five episodes of hypoglycemia and three episodes of hyperglycemia. All the CGMVs indicating hyperglycemia matched with the blood sample taken via the point-of-care glucometer. Conclusions: The use of a CGMS would be useful as it could detect more episodes of disglycemia than standard care. Our data show poor results in terms of the accuracy of the CGMS in this particular setting. Full article

We performed a retrospective, observational study of 51 eyes in 51 treatment-naïve patients with polypoidal choroidal vasculopathy (PCV), whose lesion ranged within the 6 × 6 mm scope of optical coherence tomography angiography (OCTA). The patients were divided into an ill-defined group and a well-defined group based on the pattern of branching vascular network (BVN) on OCTA. BVN morphology was not related to baseline best-corrected visual acuity (BCVA). However, the BCVA in the ill-defined BVN group (−0.18 [interquartile range: −0.40 to 0.00]) was significantly improved after anti-vascular endothelial growth factor (VEGF) injections, compared with that (0.00 [interquartile range: −0.18 to 0.00]) in the well-defined group (z = 2.143, p = 0.032). Multiple logistic regression analysis showed that male sex, fewer injections, and the presence of polypoidal lesions on OCTA images at baseline predicted a poor prognosis in patients with polypoidal lesions on OCTA images after anti-VEGF therapy (all p < 0.05). Finally, BCVA at baseline and the number of injections were protective factors for BCVA after anti-VEGF therapy (all p < 0.05). In contrast, a history of hypertension and macular edema at baseline were risk factors for BCVA after anti-VEGF injections (all p < 0.05). Our results revealed the visual and morphological prognosis of patients with active subfoveal circumscribed PCV after anti-VEGF therapy. Full article

Background: Numerous mortality prediction tools are currently available to assist patients with moderate to severe traumatic brain injury (TBI). However, an algorithm that utilizes various machine learning methods and employs diverse combinations of features to identify the most suitable predicting outcomes of brain injury patients in the intensive care unit (ICU) has not yet been well-established. Method: Between January 2016 and December 2021, we retrospectively collected data from the electronic medical records of Chi Mei Medical Center, comprising 2260 TBI patients admitted to the ICU. A total of 42 features were incorporated into the analysis using four different machine learning models, which were then segmented into various feature combinations. The predictive performance was assessed using the area under the curve (AUC) of the receiver operating characteristic (ROC) curve and validated using the Delong test. Result: The AUC for each model under different feature combinations ranged from 0.877 (logistic regression with 14 features) to 0.921 (random forest with 22 features). The Delong test indicated that the predictive performance of the machine learning models is better than that of traditional tools such as APACHE II and SOFA scores. Conclusion: Our machine learning training demonstrated that the predictive accuracy of the LightGBM is better than that of APACHE II and SOFA scores. These features are readily available on the first day of patient admission to the ICU. By integrating this model into the clinical platform, we can offer clinicians an immediate prognosis for the patient, thereby establishing a bridge for educating and communicating with family members. Full article

Dielectric characterization has significant potential in several medical applications, providing valuable insights into the electromagnetic properties of biological tissues for disease diagnosis, treatment planning, and monitoring of therapeutic interventions. This work presents the use of a custom-designed electromagnetic characterization system, based on an open-ended coaxial probe, for discriminating between benign and malignant breast tissues in a clinical setting. The probe’s development involved a well-balanced compromise between physical feasibility and its combined use with a reconstruction algorithm known as the virtual transmission line model (VTLM). Immediately following the biopsy procedure, the dielectric properties of the breast tissues were reconstructed, enabling tissue discrimination based on a rule-of-thumb using the obtained dielectric parameters. A comparative analysis was then performed by analyzing the outcomes of the dielectric investigation with respect to conventional histological results. The experimental procedure took place at Complejo Hospitalario Universitario de Toledo—Hospital Virgen de la Salud, Spain, where excised breast tissues were collected and subsequently analyzed using the dielectric characterization system. A comprehensive statistical evaluation of the probe’s performance was carried out, obtaining a sensitivity, specificity, and accuracy of 81.6%, 61.5%, and 73.4%, respectively, compared to conventional histological assessment, considered as the gold standard in this investigation. Full article

In the context of liver surgery, predicting postoperative liver dysfunction is essential. This study explored the potential of preoperative liver function assessment by MRI for predicting postoperative liver dysfunction and compared these results with the established indocyanine green (ICG) clearance test. This prospective study included patients undergoing liver resection with preoperative MRI planning. Liver function was quantified using T1 relaxometry and correlated with established liver function scores. The analysis revealed an improved model for predicting postoperative liver dysfunction, exhibiting an accuracy (ACC) of 0.79, surpassing the 0.70 of the preoperative ICG test, alongside a higher area under the curve (0.75). Notably, the proposed model also successfully predicted all cases of liver failure and showed potential in predicting liver synthesis dysfunction (ACC 0.78). This model showed promise in patient survival rates with a Hazard ratio of 0.87, underscoring its potential as a valuable tool for preoperative evaluation. The findings imply that MRI-based assessment of liver function can provide significant benefits in the early identification and management of patients at risk for postoperative liver dysfunction. Full article

High-resolution intraoperative PET/CT specimen imaging, coupled with prostate-specific membrane antigen (PSMA) molecular targeting, holds great potential for the rapid ex vivo identification of disease localizations in high-risk prostate cancer patients undergoing surgery. However, the accurate analysis of radiotracer uptake would require time-consuming manual volumetric segmentation of 3D images. The aim of this study was to test the feasibility of using machine learning to perform automatic nodal segmentation of intraoperative ⁶⁸Ga-PSMA-11 PET/CT specimen images. Six (n = 6) lymph-nodal specimens were imaged in the operating room after an e.v. injection of 2.1 MBq/kg of ⁶⁸Ga-PSMA-11. A machine learning-based approach for automatic lymph-nodal segmentation was developed using only open-source Python libraries (Scikit-learn, SciPy, Scikit-image). The implementation of a k-means clustering algorithm (n = 3 clusters) allowed to identify lymph-nodal structures by leveraging differences in tissue density. Refinement of the segmentation masks was performed using morphological operations and 2D/3D-features filtering. Compared to manual segmentation (ITK-SNAP v4.0.1), the automatic segmentation model showed promising results in terms of weighted average precision (97–99%), recall (68–81%), Dice coefficient (80–88%) and Jaccard index (67–79%). Finally, the ML-based segmentation masks allowed to automatically compute semi-quantitative PET metrics (i.e., SUVmax), thus holding promise for facilitating the semi-quantitative analysis of PET/CT images in the operating room. Full article

Distant metastasis of cholangiocarcinoma is most commonly diagnosed in the liver; however, it can also be found in the lungs, distant lymph nodes, bones, and brain. Distant lymph node metastasis outside the abdominal region without concurrent abdominal metastasis is exceedingly rare in extrahepatic cholangiocarcinoma. Herein, we present interesting ¹⁸F-FDG PET/CT images of a 49-year-old male patient with common bile duct cancer. In this case, the patient, who was scheduled for surgery, unexpectedly showed axillary lymph node metastasis on a preoperative ¹⁸F-FDG PET scan, which was subsequently confirmed via histological examination. Although such cases are exceptionally rare, this accurate diagnosis prompted a modification of the treatment plan, leading to a positive therapeutic response. Full article

It is rare to use the one-stage model without segmentation for the automatic detection of coronary lesions. This study sequentially enrolled 200 patients with significant stenoses and occlusions of the right coronary and categorized their angiography images into two angle views: The CRA (cranial) view of 98 patients with 2453 images and the LAO (left anterior oblique) view of 176 patients with 3338 images. Randomization was performed at the patient level to the training set and test set using a 7:3 ratio. YOLOv5 was adopted as the key model for direct detection. Four types of lesions were studied: Local Stenosis (LS), Diffuse Stenosis (DS), Bifurcation Stenosis (BS), and Chronic Total Occlusion (CTO). At the image level, the precision, recall, [email protected], and [email protected] predicted by the model were 0.64, 0.68, 0.66, and 0.49 in the CRA view and 0.68, 0.73, 0.70, and 0.56 in the LAO view, respectively. At the patient level, the precision, recall, and F₁scores predicted by the model were 0.52, 0.91, and 0.65 in the CRA view and 0.50, 0.94, and 0.64 in the LAO view, respectively. YOLOv5 performed the best for lesions of CTO and LS at both the image level and the patient level. In conclusion, the one-stage model without segmentation as YOLOv5 is feasible to be used in automatic coronary lesion detection, with the most suitable types of lesions as LS and CTO. Full article

Background: The rapid detection of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is vital for patient care. The LumiraDx™ SARS-CoV-2 RNA Star Complete (RSC) is an Emergency Use Authorization-recognized molecular test using nasal/nasopharyngeal swabs immersed in a viral/universal transport medium (VTM/UTM). However, there is a critical need for an alternative medium for point-of-care testing (POCT). This study aimed to investigate Xtract-Free (XF), a novel collection medium for transport and direct (extraction-free) use with nucleic acid tests. Methods: Using serially diluted SARS-CoV-2 viral RNA (vRNA) in a routine UTM and XF, a limit of detection (LOD) was established via an RSC test and a quantitative reverse transcription PCR (RT-qPCR). Additionally, the results obtained from a panel of 108 clinical “car-side” nasal swabs collected in XF during the coronavirus pandemic and assessed using the ”gold-standard” RT-qPCR assay were compared to Lumira’s RSC assay. Results: The average replicate RT-qPCR cycle threshold (C_T) values for vRNA in XF and UTM were observed to be equivalent. An LOD for which five out of five replicates were detected using XF or VTM was approximately 2000 copies/mL. The nasal swabs collected in XF exhibited 93.9% positive percent agreement (sensitivity) and 100% negative percent agreement (specificity) compared to the RT-qPCR. Three specimens tested positive via an RT-qPCR were negative when tested via RSC; however, all three samples had C_T values ≥ 36.4. Conclusions: XF is equivalent to VTM/UTM and is compatible for use with the RSC test. Furthermore, XF can be used directly with RT-qPCRs and rapid antigen testing without the requirement for separate nucleic acid extraction (an extraction-free process), making it ideal for cost-effective high-throughput and decentralized respiratory testing. Impact Statement: This study is the first to evaluate LumiraDx’s SARS-CoV-2 RNA Star Complete assay in concert with Xtract-Free (XF), a novel collection medium containing a proprietary RNase-inactivating technology for the rapid, ”extraction-free” detection of SARS-CoV-2 RNA from clinical nasal swabs. Specimens collected in XF combined with rapid LumiraDx detection provide a safe and sensitive alternative to VTM/UTM, and Molecular Transport medium (MTM) for high throughput, “extraction-free” molecular detection. Full article

The objectives of this retrospective study were to measure the prevalence of complete ponticulus posticus (CPP), to propose a new classification based on two different shapes of CPP, to compare these shapes with age and gender, and to test two different methods of measurements of the diameters of CPP on cone beam computed tomography (CBCT). Material and methods: We used 2012 CBCT scans from Planmeca Promax 3D Mid and Romexis 5.1 software tools to measure the height and width of the CPP, and we measured the surface of the CPP using an ellipse tool. We classified the CPP into “thin” and “thick” shape. Results: the prevalence of CPP was 9.49% with 97 male and 94 female patients. The unilateral type was found in 131 patients, while the bilateral type was found in 60 patients. Intra-observer reliability was evaluated using the intraclass correlation coefficient (ICC). The ICC was 0.875 for height, 0.872 for width, and 0.885 for the ellipse area. Both methods present very good intra-observer reproducibility. The “thin” group tended to be older and significantly more related to female patients. The “thick” group was associated with younger male patients. Conclusions: the proposed classification of CPP may be used when reporting the CBCT large field of view. There is still a need to increase the knowledge on the atlas and on its main variant, such as complete PP. Full article

Thyroid cancer is the most common malignancy of the endocrine system. Fine-needle aspiration (FNA) biopsy of thyroid nodules has become the gold standard procedure, in terms of cost and efficacy, for guiding clinicians towards appropriate patients’ management. One challenge for cytopathologists is to accurately classify cytological specimens as benign or malignant based on cytomorphological features. In fact, with a frequency ranging from 10% to 30%, nodules are diagnosed as indeterminate. In recent years, the mutational landscape of thyroid tumors has been extensively described, and two molecular profiles have been identified: RAS-like (NRAS, HRAS, and KRAS mutations; EIF1AX mutations; BRAF K601E mutation; and PPARG and THADA fusions) and BRAF^V600E-like (including BRAF^V600E mutation and RET and BRAF fusions). The purpose of this review is to discuss the latest molecular findings in the context of indeterminate thyroid nodules, highlighting the role of molecular tests in patients’ management. Full article

Uncontrolled and fast cell proliferation is the cause of brain tumors. Early cancer detection is vitally important to save many lives. Brain tumors can be divided into several categories depending on the kind, place of origin, pace of development, and stage of progression; as a result, tumor classification is crucial for targeted therapy. Brain tumor segmentation aims to delineate accurately the areas of brain tumors. A specialist with a thorough understanding of brain illnesses is needed to manually identify the proper type of brain tumor. Additionally, processing many images takes time and is tiresome. Therefore, automatic segmentation and classification techniques are required to speed up and enhance the diagnosis of brain tumors. Tumors can be quickly and safely detected by brain scans using imaging modalities, including computed tomography (CT), magnetic resonance imaging (MRI), and others. Machine learning (ML) and artificial intelligence (AI) have shown promise in developing algorithms that aid in automatic classification and segmentation utilizing various imaging modalities. The right segmentation method must be used to precisely classify patients with brain tumors to enhance diagnosis and treatment. This review describes multiple types of brain tumors, publicly accessible datasets, enhancement methods, segmentation, feature extraction, classification, machine learning techniques, deep learning, and learning through a transfer to study brain tumors. In this study, we attempted to synthesize brain cancer imaging modalities with automatically computer-assisted methodologies for brain cancer characterization in ML and DL frameworks. Finding the current problems with the engineering methodologies currently in use and predicting a future paradigm are other goals of this article. Full article

We report a rare case of spindle cell rhabdomyosarcoma. Sarcomas generally exhibit an abnormal increased FDG uptake on ¹⁸F-FDG PET/CT imaging, while spindle cell rhabdosarcomas exhibits a significantly increased lesion uptake on ⁶⁸Ga FAPI PET/CT imaging compared to ¹⁸F-FDG. This case suggests that ⁶⁸Ga-FAPI PET/CT has potential value in evaluating spindle cell rhabdomyosarcoma. Full article

Histological and naked-eye dissections are frequently used to investigate human anatomy. However, limitations of conventional methods include tissue damage and difficulty in observing structures, rendering findings limited. Micro-computed tomography (micro-CT) allows for a three-dimensional observation with whole-mount staining for contrast enhancement. A precise anatomical understanding of the larynx is essential for both the medical and surgical fields; however, the larynx is difficult to dissect because of its minuscule and complex structures. Therefore, we aimed to clarify the detailed anatomy of the larynx using micro-CT. The study was conducted on twelve specimens of cadavers using Lugol-based-contrast micro-CT. Using Lugol-micro-CT, relevant information on human structures was obtained. Consequently, we successfully employed the Lugol-micro-CT technique in the analysis of specific human soft tissue structures that are challenging to analyze using conventional methods. Full article

Background: Palpation, a traditional haptic ability, is used daily by practitioners of all medical and surgical specialties to assess patients. In the current study, one of the authors, in a routine clinical setting, was able to deduce the dynamic features of the putative inferior belly of omohyoid. This led to a proof-of-concept study that yielded results consistent with the clinical findings. Methods: The first part of the study involved a survey of 300 rheumatic disease patients in whom the greater supraclavicular fossa was explored by palpation. While the patient kept the head straight, the clinician placed his middle three fingers 2.5–3 cm dorsal to the clavicle in the window between the sternocleidomastoid and trapezius clavicular insertions, explored the supraclavicular fossa, and palpated the paired contractile inferior belly of the assumed omohyoid during flexion in the three orthogonal planes. In the second part of the study, five normal subjects were examined in a similar manner by the same clinician and had independent ultrasonography performed on the dominant side. Descriptive statistics were used, and Yates’ corrected chi-squared test was applied to certain nominal variables. Additionally, a comparative anterolateral bilateral neck dissection was performed in a cadaveric specimen. Results: Both studies showed that the contractile structure was the inferior belly of omohyoid and that its contraction occurred during anterior neck flexion and was opposite to the side of neck rotation, resembling the sternocleidomastoid. Conclusions: Palpation uncovered a previously unknown function of the inferior belly of omohyoid, suggesting that physical examination of the musculoskeletal system based on palpation may lead to hypotheses worthy of exploration. Full article

Although interventional radiology (IVR) is preferred over surgical procedures because it is less invasive, it results in increased radiation exposure due to long fluoroscopy times and the need for frequent imaging. Nurses engaged in cardiac IVR receive the highest lens radiation doses among medical workers, after physicians. Hence, it is important to measure the lens exposure of IVR nurses accurately. Very few studies have evaluated IVR nurse lens doses using direct dosimeters. This study was conducted using direct eye dosimeters to determine the occupational eye dose of nurses engaged in cardiac IVR, and to identify simple and accurate methods to evaluate the lens dose received by nurses. Over 6 months, in a catheterization laboratory, we measured the occupational dose to the eyes (3 mm dose equivalent) and neck (0.07 mm dose equivalent) of nurses on the right and left sides. We investigated the relationship between lens and neck doses, and found a significant correlation. Hence, it may be possible to estimate the lens dose from the neck badge dose. We also evaluated the appropriate position (left or right) of eye dosimeters for IVR nurses. Although there was little difference between the mean doses to the right and left eyes, that to the right eye was slightly higher. In addition, we investigated whether it is possible to estimate doses received by IVR nurses from patient dose parameters. There were significant correlations between the measured doses to the neck and lens, and the patient dose parameters (fluoroscopy time and air kerma), implying that these parameters could be used to estimate the lens dose. However, it may be difficult to determine the lens dose of IVR nurses accurately from neck badges or patient dose parameters because of variation in the behaviors of nurses and the procedure type. Therefore, neck doses and patient dose parameters do not correlate well with the radiation eye doses of individual IVR nurses measured by personal eye dosimeters. For IVR nurses with higher eye doses, more accurate measurement of the radiation doses is required. We recommend that a lens dosimeter be worn near the eyes to measure the lens dose to IVR nurses accurately, especially those exposed to relatively high doses. Full article

Pelvic floor muscles (PFMs) play a crucial role in maintaining pelvic organ support and continence. However, pelvic floor dysfunction (PFD), often resulting from insufficient PFM control, poses a substantial global health challenge for women. This study aims to explore the relationship between levator ani muscle elasticity when assessed through transperineal shear-wave elastography (SWE) and bladder base displacement, quantified using transabdominal ultrasonography (TAUS), as a means to comprehensively evaluate PFM function. A total of 42 nulliparous women participated in this study. Participants received instructions on proper PFM contractions using Kegel exercises. Levator ani muscle elasticity was assessed both at rest and during contractions using transperineal SWE, while bladder base displacement was simultaneously measured through TAUS. Repeated measures demonstrated strong intraclass correlation coefficients of 0.906 at rest and 0.687 during contractions for levator ani muscle elasticity. The mean elasticity values were 24.7 ± 4.5 kPa at rest and 62.1 ± 10.4 kPa during contractions. Additionally, the mean bladder base displacement was 7.2 ± 2.5 mm, and the normalized bladder base displacement via body mass index was 0.3 ± 0.1 mm. Significantly, a moderate correlation was identified between the PFM function, represented by the difference in levator ani elasticity during contractions and resting, and bladder base displacement (r = 0.486, p = 0.001). These findings underscore the potential utility of transperineal SWE as a reliable and noninvasive method to assess levator ani muscle elasticity and, consequently, PFM function. In conclusion, this study sheds light on the interplay between PFM elasticity and bladder base displacement, offering insights into PFM function assessments. The observed correlation suggests the clinical relevance of SWE in providing valuable information for treatment planning in PFD. These findings contribute to a deeper understanding of PFM dynamics, ultimately aiding in the effective management of PFD among women. Full article

After three years of the SARS-CoV-2 pandemic, the demand for developing field-deployable point-of-care (PoC) molecular diagnostic tests has increased. Although RT-qPCR is the molecular diagnostic gold standard and is accurate, it is not readily applied to point-of-care testing (POCT). Meanwhile, rapid diagnostic kits have the disadvantage of low sensitivity. Recently, rapid isothermal nucleic acid amplification technology has emerged as an alternative for rapid diagnosis. Here, we developed a rapid SARS-CoV-2 reverse transcription loop-mediated isothermal amplification (RT-LAMP)-lateral flow assay (LFA) kit. This kit includes a Chelex-100/boiling nucleic acid extraction device and a one-step amplification detection apparatus capable of performing the entire process, from RNA extraction to detection, and diagnosing SARS-CoV-2 infection within 40 min without contamination. The detection limits of the rapid SARS-CoV-2 RT-LAMP-LFA kit were 100 plaque-forming units (PFUs) mL⁻¹ and 10⁻¹ PFU mL⁻¹ for RNA samples extracted using the Chelex-100/boiling nucleic acid extraction device and commercial AdvansureTM E3 system, respectively. The sensitivity and specificity of the rapid SARS-CoV-2 RT-LAMP-LFA kit were 97.8% and 100%, respectively. Our SARS-CoV-2 RT-LAMP-LFA kit exhibited high sensitivity and specificity within 40 min without requiring laboratory instruments, suggesting that the kit could be used as a rapid POC molecular diagnostic test for SARS-CoV-2. Full article

(1) Introduction: Sentinel lymph node biopsy (SLNB) is widely used in breast cancer patients who undergo neoadjuvant chemotherapy (NAC), replacing axillary lymph node dissection. While commonly accepted for cN0 patients, its role in cN1/2 patients remains controversial. Our study aims to investigate the role of SLNB in BC patients who underwent prior NAC and compare our results to those of other studies presented in the literature. (2) Materials and methods: Our retrospective study included 102 breast cancer patients who received NAC before ^99mTc-albumin Nanocolloid SLN mapping and SLNB was performed, completed or not with axillary dissection. A review based on the PRISMA statement was also carried out, encompassing 20 studies. (3) Results: The lymphoscintigraphy performed after the administration of NAC presented an identification rate (IR) of 93.13%. IR for SLNB was 94.11%, with a false-negative rate (FNR) of 7.4%. After a median follow-up of 31.3 months, we obtained a distant disease-free survival rate of 98%. The results obtained by other groups were similar to those of our study, presenting IR in the range 80.8–96.8%, with FNR varying from 0 to 22%. (4) Conclusions: on conclusion, SLNB can accurately determine the lymph node status, with an acceptable FNR and maintain its expected prognostic role with low recurrence rates, and our results are comparable to those obtained by other studies. Full article

Autoantibodies against specific lung cancer-associated antigens have been suggested for the performance of lung cancer diagnosis. This study aimed to evaluate the diagnostic performance of the antigen–autoantibody immune complex (AIC) against its free antigens for CYFRA21-1, ProGRP, neutrophil gelatinase-associated lipocalin (NGAL), and neuron-specific enolase (NSE) in non-small cell lung cancer (NSCLC). In total, 85 patients with NSCLC and 120 healthy controls (HCs) were examined using a 9-guanine DNA chip method. The ratios of AICs to their antigens and the combinations of ratios consisting of two to four markers were calculated. The levels of AICs for CYFRA21-1, ProGRP, NGAL, and NSE were higher than those for their free antigens in all participants. The levels of each free antigens distinguished patients with NSCLC from the HCs. The ratios of the AIC to its antigen and seven combinations of two to four ratios were significantly higher in patients with NSCLC than in the HCs. Excellent diagnostic performance was observed for all combination ratios (C4-1), with 85.9% sensitivity and 86.7% specificity at a 3.51 cut-off. Higher sensitivity was observed in the early stages (0–I) and adenocarcinoma than in stages II–IV and other pathological types. Combining all ratios of AICs and their antigens for all four markers was useful when diagnosing NSCLC. Full article

Purpose: To characterize the magnetic resonance imaging features of primary intrahepatic lymphoepithelioma-like cholangiocarcinoma (LELCC). Materials and Methods: Thirty-four patients with 38 histologically confirmed LELCCs were enrolled retrospectively from January 2014 to August 2022. We evaluated the clinical features, histologic findings, and imaging manifestations on dynamic enhanced MRI. Results: 74% (25/34) of the cases were associated with EBV infection. Moreover, patients infected with EBV exhibited a lower level of Ki-67 proliferation. The serum CA199 level was elevated in 10 patients. The median tumor diameter was 2.8 cm (range, 1.1–8.7 cm). Most tumors were well-defined with a smooth or lobulated margin and showed peripheral hyperintensity and central hypointensity on T2-weighted imaging (T2WI). T2 hyperintense foci were recognized in 8 patients. In the dynamic enhanced MRI, 21 tumors demonstrated Type A enhancement pattern (rim enhancement), 10 demonstrated Type B (rapid wash-in and wash-out), and seven demonstrated Type C (rapid wash-in without wash-out). Capsular enhancement in PVP or DP was found in 22 tumors. A few patients had satellite lesions, portal vein thrombosis, bile duct dilatation, and distal metastasis. Lymph node metastases were discovered pathologically in 11 patients. Conclusions: MRI findings of LELCC vary and are non-specific. While a majority of LELCCs exhibit typical features of intrahepatic cholangiocarcinoma (iCCA), unique findings like T2 hyperintense foci or capsular enhancement could suggest LELCC. EBV infection and elevated tumor markers can aid in differentiation. However, given the mimics of some cases of liver hypervascular lesions, histological examination remains essential for definitive diagnosis. Full article

Background: The over-the-scope clip (OTSC) is a highly effective clipping device for refractory gastrointestinal disease. However, Japanese data from multicenter studies for anastomotic leakage (AL) involving a secondary fistula after gastrointestinal surgery are lacking. Therefore, this study evaluated the efficacy and safety of OTSC placement in Japanese patients with such conditions. Methods: We retrospectively collected data from 28 consecutive patients from five institutions who underwent OTSC-mediated closure for AL between July 2017 and July 2020. Results: The AL and fistula were located in the esophagus (3.6%, n = 1), stomach (10.7%, n = 3), small intestine (7.1%, n = 2), colon (25.0%, n = 7), and rectum (53.6%, n = 15). The technical success, clinical success, and complication rates were 92.9% (26/28), 71.4% (20/28), and 0% (0/28), respectively. An age of <65 years (85.7%), small intestinal AL (100%) and colonic AL (100%), defect size of <10 mm (82.4%), time to OTSC placement > 7 days (84.2%), and the use of simple suction (78.9%) and anchor forceps (80.0%) were associated with higher clinical success rates. Conclusion: OTSC placement is a useful therapeutic option for AL after gastrointestinal surgery. Full article

The liver plays an important role in normal metabolism and physiological functions such as acid-base balance; however, limited epidemiologic studies have investigated how the liver contributes toward acid-base balance using non-invasive biomarkers. We determined associations between serum biomarkers related to acid-base balance and renal function with liver CYP1A2 activity. We used data from 1381 participants of the 2009–2010 National Health and Nutrition Examination Survey (NHANES) with measurements of serum phosphorus, serum bicarbonate, caffeine intake, caffeine metabolites, and estimated glomerular filtration rate (eGFR). Liver CYP1A2 activity was estimated using urine caffeine metabolite indices, which were calculated as the ratio of one of the urine caffeine metabolites (i.e., paraxanthine and 1-methyluric acid) to caffeine intake. We analyzed associations in the whole data set and in different strata of hepatic steatosis index (HSI) based on different cut-points. We found that serum bicarbonate was positively associated with CYP1A2 activity in the whole data set when comparing persons with bicarbonate at Q4 to Q1 (β = 0.18, p = 0.10 for paraxanthine; β = 0.20, p = 0.02 for 1-methyluric acid). Furthermore, serum phosphorus was positively associated with CYP1A2 activity only in the stratum of 30 ≤ HSI < 36. Lastly, low eGFR was significantly associated with lower CYP1A2 activity measured with paraxanthine in the whole dataset and in all the strata with HSI < 42; when comparing eGFR < 60 to eGFR > 90, β estimates ranged from −0.41 to −1.38, p-values ranged from 0.0018 to 0.004. We observed an opposite trend in the highest stratum (HSI ≥ 42). Non-invasive measurements of serum bicarbonate, serum phosphorus, and eGFR have dynamic associations with CYP1A2 activity. These associations depend on the extent of liver damage and the caffeine metabolite used to assess CYP1A2 activity. Full article

Background: Chest X-ray (CXR) remains the standard imaging modality in postoperative care after non-cardiac thoracic surgery. Lung ultrasound (LUS) showed promising results in CXR reduction. The aim of this review was to identify areas where the evaluation of LUS videos by artificial intelligence could improve the implementation of LUS in thoracic surgery. Methods: A literature review of the replacement of the CXR by LUS after thoracic surgery and the evaluation of LUS videos by artificial intelligence after thoracic surgery was conducted in Medline. Results: Here, eight out of 10 reviewed studies evaluating LUS in CXR reduction showed that LUS can reduce CXR without a negative impact on patient outcome after thoracic surgery. No studies on the evaluation of LUS signs by artificial intelligence after thoracic surgery were found. Conclusion: LUS can reduce CXR after thoracic surgery. We presume that artificial intelligence could help increase the LUS accuracy, objectify the LUS findings, shorten the learning curve, and decrease the number of inconclusive results. To confirm this assumption, clinical trials are necessary. This research is funded by the Slovak Research and Development Agency, grant number APVV 20-0232. Full article

Background: The aim of our study was to evaluate the diagnostic capacity of the tear meniscus osmolarity measurement for dry eye disease (DED) in patients with rheumatoid arthritis (RA), using a portable osmometer based on electrical impedance and an integrated circuit technology (TearLab^® (Escondido, CA, USA)). Methods: We included 101 RA patients, 81 patients with DED and 20 without DED (controls). We measured tear osmolarity and assessed other clinical diagnostic tests as suggested by the TFOS DEWS II composite reference standard diagnostic criteria for DED using Ocular Surface Disease Index (OSDI), Five-item Dry Eye Questionnaire (DEQ-5), fluorescein tear break-up time (F-TUBT), ocular surface staining (SICCA score), and other clinical parameters to classify DED subtypes. We analyzed the agreement between osmolarity and the TFOS DEWS II composite reference standard for DED diagnosis. We conducted receiver operating characteristic (ROC) curve analyses using the DED variable and its subtypes as dependent variables and the continuous variable for osmolarity or the inter-eye difference in osmolarity as independent variable. Sensitivity, specificity, and area under the curve for all potential cut-off points were obtained and reported from ROC curves. Results: We found that tear meniscus osmolarity had a low diagnostic capacity for DED (AUC = 0.57). Tear meniscus osmolarity measurement had a sensitivity of 35% and a specificity of 80% with a kappa level of agreement of 0.08 compared to the TFOS DEWS II composite reference standard. The low diagnostic capacity of the tear meniscus osmolarity was similar for aqueous-deficient DED and for evaporative DED, being only fair for severe DED with a 57% sensitivity and 80% specificity and a kappa level of agreement of 0.36. Conclusions: Our findings suggest that in patients with RA, tear meniscus osmolarity measured by the TearLab^® showed low sensitivity, low specificity, and limited agreement with the TFOS DEWS II composite reference standard for DED diagnosis. Full article

Purpose: Next-generation sequencing (NGS) technology detects specific mutations that can provide treatment opportunities for colorectal cancer (CRC) patients. Patients and Methods: We analyzed the mutation frequencies of common actionable genes and their association with clinicopathological characteristics and oncologic outcomes using targeted NGS in 107 Saudi Arabian patients without a family history of CRC. Results: Approximately 98% of patients had genetic alterations. Frequent mutations were observed in BRCA2 (79%), CHEK1 (78%), ATM (76%), PMS2 (76%), ATR (74%), and MYCL (73%). The APC gene was not included in the panel. Statistical analysis using the Cox proportional hazards model revealed an unusual positive association between poorly differentiated tumors and survival rates (p = 0.025). Although no significant univariate associations between specific mutations or overall mutation rate and overall survival were found, our preliminary analysis of the molecular markers for CRC in a predominantly Arab population can provide insights into the molecular pathways that play a significant role in the underlying disease progression. Conclusions: These results may help optimize personalized therapy when drugs specific to a patient’s mutation profile have already been developed. Full article

Background: The integration of artificial intelligence (AI) into various fields has ushered in a new era of multidisciplinary progress. Defined as the ability of a system to interpret external data, learn from it, and adapt to specific tasks, AI is poised to revolutionize the world. In forensic medicine and pathology, algorithms play a crucial role in data analysis, pattern recognition, anomaly identification, and decision making. This review explores the diverse applications of AI in forensic medicine, encompassing fields such as forensic identification, ballistics, traumatic injuries, postmortem interval estimation, forensic toxicology, and more. Results: A thorough review of 113 articles revealed a subset of 32 papers directly relevant to the research, covering a wide range of applications. These included forensic identification, ballistics and additional factors of shooting, traumatic injuries, post-mortem interval estimation, forensic toxicology, sexual assaults/rape, crime scene reconstruction, virtual autopsy, and medical act quality evaluation. The studies demonstrated the feasibility and advantages of employing AI technology in various facets of forensic medicine and pathology. Conclusions: The integration of AI in forensic medicine and pathology offers promising prospects for improving accuracy and efficiency in medico-legal practices. From forensic identification to post-mortem interval estimation, AI algorithms have shown the potential to reduce human subjectivity, mitigate errors, and provide cost-effective solutions. While challenges surrounding ethical considerations, data security, and algorithmic correctness persist, continued research and technological advancements hold the key to realizing the full potential of AI in forensic applications. As the field of AI continues to evolve, it is poised to play an increasingly pivotal role in the future of forensic medicine and pathology. Full article

(1) Background: Treating female pelvic organ prolapse (POP) is challenging. Surgical meshes have been used in transvaginal surgeries since the 1990s, but complications such as mesh exposure and infection have been reported. Polyvinylidene fluoride (PVDF) mesh, known for its stability and non-reactive properties, has shown promise in urogynecological surgeries. (2) Methods: A retrospective analysis was conducted on 27 patients who underwent a modified PVDF vaginal mesh repair procedure using DynaMesh^®-PR4 and combined trans-obturator and sacrospinous fixation techniques. Additional surgeries were performed as needed. (3) Results: The mean operation time was 56.7 min, and the mean blood loss was 66.7 mL. The average hospitalization period was 4.2 days with Foley catheter removal after 2 days. Patients experienced lower pain scores from the day of the operation to the following day. Postoperative follow-up revealed that 85.2% of patients achieved anatomic success, with 14.8% experiencing recurrent stage II cystocele. No recurrence of apical prolapse was observed. Complications were rare, with one case (3.7%) of asymptomatic mesh protrusion. (4) Conclusions: The modified vaginal mesh procedure using DynaMesh^®-PR4 showed favorable outcomes with a short operation time, low recurrence rate, rare complications, and improved functional outcomes. This surgical option could be considered for anterior and apical pelvic organ prolapse in women. Full article