An approach to the diagnosis of lumbar disc herniation using deep learning models.

Background: In magnetic resonance imaging (MRI), lumbar disc herniation (LDH) detection is challenging due to the various shapes, sizes, angles, and regions associated with bulges, protrusions, extrusions, and sequestrations. Lumbar abnormalities in MRI can be detected automatically by using deep learning methods. As deep learning models gain recognition, they may assist in diagnosing LDH with MRI images and provide initial interpretation in clinical settings. YOU ONLY LOOK ONCE (YOLO) model series are often used to train deep learning algorithms for real-time biomedical image detection and prediction. This study aims to confirm which YOLO models (YOLOv5, YOLOv6, and YOLOv7) perform well in detecting LDH in different regions of the lumbar intervertebral disc. Materials and methods: The methodology involves several steps, including converting DICOM images to JPEG, reviewing and selecting MRI slices for labeling and augmentation using ROBOFLOW, and constructing YOLOv5x, YOLOv6, and YOLOv7 models based on the dataset. The training dataset was combined with the radiologist's labeling and annotation, and then the deep learning models were trained using the training/validation dataset. Results: Our result showed that the 550-dataset with augmentation (AUG) or without augmentation (non-AUG) in YOLOv5x generates satisfactory training performance in LDH detection. The AUG dataset overall performance provides slightly higher accuracy than the non-AUG. YOLOv5x showed the highest performance with 89.30% mAP compared to YOLOv6, and YOLOv7. Also, YOLOv5x in non-AUG dataset showed the balance LDH region detections in L2-L3, L3-L4, L4-L5, and L5-S1 with above 90%. And this illustrates the competitiveness of using non-AUG dataset to detect LDH. Conclusion: Using YOLOv5x and the 550 augmented dataset, LDH can be detected with promising both in non-AUG and AUG dataset. By utilizing the most appropriate YOLO model, clinicians have a greater chance of diagnosing LDH early and preventing adverse effects for their patients.

Combination of Autologous Fat Grafting and Negative-Pressure Wound Therapy for the Treatment of Scalp Linear Scleroderma.

ABSTRACT: Scalp linear scleroderma (LSc) is a subtype of localized scleroderma which typically affects young patients and which can be severely disfiguring. Traditional treatment options include bone grafting or tissue expansion. in this report, we present the case of a patient with scalp LSc successfully treated with scar release, autologous fat grafting, and negative-pressure wound therapy (NPWT). A 55-year-old female, with a history of craniectomy for a benign sellar tumor 10 years previously, developed LSc over the frontal scalp with exposure of titanium plates and screws. She was treated with removal of metalwork, scar release, autologous fat grafting from the abdominal wall and immediate application of NPWT. At 3-month postoperative follow-up, the appearance of the depressed lesion and of its margins had significantly improved. Our experience suggests that the combination of autologous fat grafting and NPWT is an effective treatment modality for scalp LSc.

Diameter Reduction Determined Through Carotid Ultrasound Associated With Cardiovascular and All-Cause Mortality: A Single-Center Experience of 38 201 Consecutive Patients in Taiwan.

Background Few studies have evaluated the prognostic significance of diameter-based carotid sonographic measurements for mortality. We investigated whether a reduction in diameter of different carotid anatomical segments is associated with cardiovascular and all-cause mortality in a hospital-based cohort with universal health care. Methods and Results We conducted a retrospective cohort study of 38 201 patients who underwent carotid duplex ultrasound at a medical center in Taiwan. Carotid sonographic parameters were the diameter reduction percentage in carotid bifurcation, the internal carotid artery, the common carotid artery, and the external carotid artery and the overall carotid atherosclerotic burden score, determined by summing the scores from all segments. The vital status was ascertained by linking data to National Death Registry until 2017. During a median follow-up of 4.2 years, 5644 participants died, with 1719 deaths attributable to cardiovascular diseases. The multivariable-adjusted hazard ratios (HRs; 95% CIs) for cardiovascular mortality were 1.33 (1.16‒1.53), 1.58 (1.361.84), and 1.89 (1.58, 2.26) for participants with 30% to <40%, 40% to <50%, and ≥50% reduction in carotid bifurcation diameter, respectively, compared with participants with <30% diameter reduction (P for trend <0.001). The corresponding HRs (95% CIs) for all-cause mortality were 1.25 (1.16‒1.34), 1.42 (1.31‒1.54), and 1.60 (1.45‒1.77), respectively. Diameter reduction at other carotid sites and the carotid atherosclerotic burden score exhibited the same dose-response relationship. Conclusions This study suggests that reduction in carotid artery diameter, which can be determined through routinely available sonography, is an independent risk factor for all-cause and cardiovascular mortality.

Bereitschaftspotential in Multiple System Atrophy.

Objective: Multiple system atrophy (MSA) is a neurodegenerative disorder manifesting as parkinsonism, cerebellar ataxia, and autonomic dysfunction. It is categorized into MSA with predominant parkinsonism (MSA-P) and into MSA with predominant cerebellar ataxia (MSA-C). The pathophysiology of motor control circuitry involvement in MSA subtype is unclear. Bereitschaftspotential (BP) is a feasible clinical tool to measure electroencephalographic activity prior to volitional motions. We recorded BP in patients with MSA-P and MSA-C to investigate their motor cortical preparation and activation for volitional movement. Methods: We included eight patients with MSA-P, eight patients with MSA-C, and eight age-matched healthy controls. BP was recorded during self-paced rapid wrist extension movements. The electroencephalographic epochs were time-locked to the electromyography onset of the voluntary wrist movements. The three groups were compared with respect to the mean amplitudes of early (1,500-500 ms before movement onset) and late (500-0 ms before movement onset) BP. Results: Mean early BP amplitude was non-significantly different between the three groups. Mean late BP amplitude in the two patient groups was significantly reduced in the parietal area contralateral to the movement side compared with that in the healthy control group. In addition, the late BP of the MSA-C group but not the MSA-P group was significantly reduced at the central parietal area compared with that of the healthy control group. Conclusions: Our findings suggest that patients with MSA exhibit motor cortical dysfunction in voluntary movement preparation and activation. The dysfunction can be practicably evaluated using late BP, which represents the cerebello-dentato-thalamo-cortical pathway.

Three-year mortality in cryptococcal meningitis: Hyperglycemia predict unfavorable outcome.

Existing evidence revealed grave prognosis for cryptococcal meningitis (CM), particularly its short-term mortality. However, its long-term survival and prognostic factors remained unknown. This study investigated 3-year mortality and analyzed its predictive factors in patients with CM. This retrospective cohort study with 83 cerebrospinal fluid culture-confirmed CM patients was conducted at China Medical University Hospital from 2003 to 2016. The 3-year mortality rate in patients with CM was 54% (45 deaths among 83 patients). Advanced age, human immunodeficiency virus (HIV) seronegative state, low Glasgow Coma Scale score on admission, decreased hemoglobin and hyperglycemia on diagnosis were associated with 3-year mortality. After multivariate adjustment in the Cox proportional hazard model, only severe hyperglycemia (serum glucose ≥200 mg/dL) on diagnosis could predict 3-year mortality.

Therapeutic Potential of Tpl2 (Tumor Progression Locus 2) Inhibition on Diabetic Vasculopathy Through the Blockage of the Inflammasome Complex.

OBJECTIVE: Diabetic retinopathy, one of retinal vasculopathy, is characterized by retinal inflammation, vascular leakage, blood-retinal barrier breakdown, and neovascularization. However, the molecular mechanisms that contribute to diabetic retinopathy progression remain unclear. Approach and Results: Tpl2 (tumor progression locus 2) is a protein kinase implicated in inflammation and pathological vascular angiogenesis. Nε-carboxymethyllysine (CML) and inflammatory cytokines levels in human sera and in several diabetic murine models were detected by ELISA, whereas liquid chromatography-tandem mass spectrometry analysis was used for whole eye tissues. The CML and p-Tpl2 expressions on the human retinal pigment epithelium (RPE) cells were determined by immunofluorescence. Intravitreal injection of pharmacological inhibitor or NA (neutralizing antibody) was used in a diabetic rat model. Retinal leukostasis, optical coherence tomography, and H&E staining were used to observe pathological features. Sera of diabetic retinopathy patients had significantly increased CML levels that positively correlated with diabetic retinopathy severity and foveal thickness. CML and p-Tpl2 expressions also significantly increased in the RPE of both T1DM and T2DM diabetes animal models. Mechanistic studies on RPE revealed that CML-induced Tpl2 activation and NADPH oxidase, and inflammasome complex activation were all effectively attenuated by Tpl2 inhibition. Tpl2 inhibition by NA also effectively reduced inflammatory/angiogenic factors, retinal leukostasis in streptozotocin-induced diabetic rats, and RPE secretion of inflammatory cytokines. The attenuated release of angiogenic factors led to inhibited vascular abnormalities in the diabetic animal model. CONCLUSIONS: The inhibition of Tpl2 can block the inflammasome signaling pathway in RPE and has potential clinical and therapeutic implications in diabetes-associated retinal microvascular dysfunction.

Type I interferon: From innate response to treatment for COVID-19.

Effective prophylactic and therapeutic interventions are urgently needed to address the coronavirus disease 2019 (COVID-19) pandemic. Various antiviral drugs have recently been tested. Type I interferon (IFN) is a regulatory protein involved in the innate immune response, with broad-spectrum antiviral activities and the ability to directly block viral replication and support the immune response to eliminate virus infection. Insufficient virus-induced type I IFN production is characteristic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, because SARS-CoV-2 suppresses the IFN response by interacting with essential IFN signaling pathways. Exogenous type I IFN is recommended for treating COVID-19. Unexpectedly however, angiotensin converting enzyme-2 (ACE2) receptor, which acts as a SARS-CoV-2 receptor, was shown to be stimulated by IFN, raising doubts about the suitability of IFN use. However, further studies have excluded concerns regarding IFN administration. Type I IFNs, including IFN-α1b, have been used clinically as antiviral drugs for many years and have shown strong antiviral activity against SARS-CoV-2 in vitro. Preliminary clinical studies of type I IFNs, especially when delivered via aerosol inhalation, have demonstrated efficacy for the treatment and prevention of COVID-19. Randomized controlled trials of IFN for COVID-19 treatment are ongoing.

Systematic review of negative pressure wound therapy for head and neck wounds with fistulas: Outcomes and complications.

Fistula formation in head and neck wounds is considered one of the most challenging complications that a head and neck reconstructive surgeon may encounter. The current mainstay of treatment is aggressive surgical debridement followed by vascularised soft tissue coverage. Negative pressure wound therapy (NPWT) has been successfully used for the closure of complicated wounds for decades. This study analysed the outcomes and complications of NPWT in the management of head and neck wounds with fistulas. A systematic search of studies published between January 1966 and September 2019 was conducted using the PubMed, MEDLINE, EMBASE, and SCOPUS databases and using the following key words: "negative pressure wound therapy," "head and neck," and "fistula." We included human studies with abstract and full text available. Analysed endpoints were rate of fistula closure, follow-up duration, and complications if present. Nine retrospective case series (Level IV evidence) that collectively included 122 head and neck wounds with orocutaneous fistulas, pharyngocutaneous fistulas, and salivary contamination were examined. The number of patients included in each study ranged from 5 to 64. The mode of NPWT varied among the included studies, with most adopting a continuous pressure of -125 mm Hg. Mean durations of NPWT ranged from 3.7 to 23 days, and the reported fistula closure rate ranged from 78% to 100%. To achieve complete wound healing, six studies used additional procedures after stopping NPWT, including conventional wound dressings and vascularised tissue transfer. Information regarding follow up was provided in only three of the nine studies, where patients were followed for 5, 10, and 18 months. No serious adverse events were reported. NPWT for head and neck wounds with fistulas may be considered a safe treatment method that yields beneficial outcomes with a low risk of complications. The current data originated mainly from studies with low levels of evidence characterised by heterogeneity. Therefore, definitive recommendations based on these data cannot be offered. Additional high-quality trials are warranted to corroborate the findings of this systematic review.

Corrigendum: Genetic Removal of the CH1 Exon Enables the Production of Heavy Chain-Only IgG in Mice.

[This corrects the article DOI: 10.3389/fimmu.2018.02202.].

Genetic Removal of the CH1 Exon Enables the Production of Heavy Chain-Only IgG in Mice.

Nano-antibodies possess great potential in many applications. However, they are naturally derived from heavy chain-only antibodies (HcAbs), which lack light chains and the CH1 domain, and are only found in camelids and sharks. In this study, we investigated whether the precise genetic removal of the CH1 exon of the γ1 gene enabled the production of a functional heavy chain-only IgG1 in mice. IgG1 heavy chain dimers lacking associated light chains were detected in the sera of the genetically modified mice. However, the genetic modification led to decreased expression of IgG1 but increased expression of other IgG subclasses. The genetically modified mice showed a weaker immune response to specific antigens compared with wild type mice. Using a phage-display approach, antigen-specific, single domain VH antibodies could be screened from the mice but exhibited much weaker antigen binding affinity than the conventional monoclonal antibodies. Although the strategy was only partially successful, this study confirms the feasibility of producing desirable nano-bodies with appropriate genetic modifications in mice.

Increased risk of overactive bladder in patients with idiopathic Parkinson's disease: Insight from a nationwide population-based cohort study.

BACKGROUND: Idiopathic Parkinson's disease (IPD) is a progressive neurodegenerative disorder characterized by typical motor impairment. However, lower urinary tract symptoms, including urinary urgency or frequency, which are non-motor phenomena, occur frequently among patients with IPD. In this study, we assess the risk of overactive bladder (OAB) in patients with IPD. METHODS: The National Health Insurance Research Database of Taiwan was used to identify patients with IPD (IPD cohort) and four-fold controls (non-IPD cohort) from 2000 to 2010. The non-IPD cohort was matched according to age, sex, and baseline comorbidities, including benign prostate hyperplasia, stress incontinence, diabetes, and cerebrovascular diseases. The occurrence of OAB was monitored until the end of 2011. Hazard ratios of OAB were estimated using Cox proportional hazards regression models. RESULTS: In total, 4,571 and 18,255 patients were included in IPD and non-IPD cohorts, respectively. Results showed a significantly higher overall incidence rate of OAB in the IPD cohort compared with the non-IPD cohort (14.5 vs. 6.37 per 10,000 person-years), with a 2.3-fold increased risk of OAB (95% confidence interval [CI] = 1.51-3.51) after controlling for benign prostate hyperplasia and stress incontinence. The mean follow-up period for the IPD cohort was 5.0 years. This cohort study showed that the cumulative incidence of OAB was 0.65% at the fifth year and 1.54% at the tenth year after IPD diagnosis; this risk was highest in the age group 65-74 years. CONCLUSION: This study reveals that IPD is independently associated with an increased risk of OAB in patients with IPD. The probability of OAB was 1.54% over a 10-year period after IPD diagnosis; the risk of OAB is considered to be age-dependent and most substantial in patients aged 65-74 years.

Coincidence or complication? A systematic review of trigger digit after carpal tunnel release.

BACKGROUND: Carpal tunnel syndrome (CTS) and trigger digits are among the most common nontraumatic hand disorders treated by plastic surgeons. The onset of trigger digits after carpal tunnel release (CTR) has been inconsistently reported. This systematic review assessed the prevalence of trigger digits development in patients after CTR surgery. METHODS: We searched the MEDLINE, EMBASE and SCOPUS databases for papers published between January 1966 and August 2016. Eligible studies contained quantitative data on the incidence of trigger digits after CTR. The primary outcome measure was the onset of trigger digits after CTR. The secondary outcome measure was the prevalence of digital involvement in patients who developed trigger digits after CTR. RESULTS: A total of 5654 CTR surgeries were performed in the included nine studies, and 483 patients (8.5%) developed trigger digits after CTR. The reported incidence of trigger digits after CTR ranged from 5.2% to 31.7%. The time to development of trigger digits was approximately 6 months postoperatively. In the eight observational studies and in the randomized controlled trial, the thumb and ring finger were reported as the most commonly involved trigger digits, respectively. CONCLUSIONS: The incidence of trigger digits after CTR surgery is not negligible. Thumbs and ring fingers are the most commonly involved digits. This topic should therefore be suitably addressed during preoperative consultations.

Incidence of trigger digits following carpal tunnel release: A nationwide, population-based retrospective cohort study.

The onset of trigger digits after carpal tunnel release (CTR) have been reported inconsistently across different studies. The aim of this study is to assess the incidence of trigger digits after CTR using nationwide population cohort data.We conducted a retrospective cohort study using the Longitudinal Health Insurance Database 2000 (LHID2000) from the National Health Insurance Database (NHIRD) in Taiwan. The LHID2000 contained 1 million beneficiaries randomly selected from the year 2000 Registry for Beneficiaries in NHIRD. We identified 2605 carpal tunnel syndrome (CTS) patients received CTR from 2000 to 2010 (CTR cohort, n = 2605). For each CTR patient, 4 CTS patients without CTR were randomly selected in the control cohort from the general population frequency matched by age, sex, and diagnosed year (non-CTR cohort, n = 10,420). Both cohorts were followed up until the end of 2011 to investigate the occurrence of trigger digits. Adjusted hazard ratios (aHRs) with 95% confidence interval (CI) of trigger digits were estimated using the Cox proportional hazards model after controlling for age, sex, and comorbidities.The CTR cohort had a mean follow-up period of 5.58 ±â€Š3.18 years and the non-CTR cohort had a mean follow-up period of 5.90 ±â€Š3.10 years. The overall risk of trigger digits was 3.63-fold greater in the CTR cohort than in the non-CTR cohort (incidence rate: 12.6 vs 3.38/1000 person-years, aHR: 3.63, 95% CI, 2.97-4.44). The incidence of postoperative trigger digits was highest in the 1st 6 months (incidence rate: 27.9/1000 person-years, aHR: 9.65, 95% CI, 5.27-17.7) and then significantly decreased over time.CTR was significantly associated with the subsequent development of trigger digits, especially in the postoperative 6 months.

Mandibular Fracture Patterns at a Medical Center in Central Taiwan: A 3-Year Epidemiological Review.

Mandibular fractures constitute a major portion of maxillofacial trauma and may lead to considerable functional and aesthetic sequelae if treatment is inadequate or delayed. An epidemiology study on mandibular fractures may guide the preventive efforts of the Taiwan public health care system. Therefore, a retrospective review was conducted at a medical center in central Taiwan to evaluate the current mandibular fracture epidemiology.The medical records and digitized radiographs of 198 patients who received treatment for mandibular fractures during a 3-year period (from October 2010 to September 2013) at a medical center in central Taiwan were reviewed to obtain demographic and injury data.The average age was 29.4 years (3-82 years). Patients aged 21 to 30 years sustained the most mandibular fractures (62 patients, 31.3%). The overall sex distribution (male to female) ratio was 1.8. Motor-vehicle accidents (MVAs) were the most common mechanism of injury (162 patients, 82%), and scooter and motorcycle riders wearing partial-coverage helmets constituted the majority of patients. A chart review identified 198 patients with 335 mandibular fractures; 113 patients (57.1%) had multiple mandibular fractures. The most common fracture sites were the symphysis and parasymphysis regions (38.9%), followed by the condyle (26.0%), angle (14.3%), body (14.3%), and ramus (6.6%).MVAs are the major cause of mandibular fractures in central Taiwan, and patients aged <30 years sustained the most mandibular fractures. Compared with previous studies, the present study has a higher percentage of women with mandibular fractures. In addition, inadequate mandibular protection by partial-coverage helmets may be a major reason for mandibular fractures most commonly localized in the symphysis and parasymphysis regions. The incidence and causes of mandibular fractures may reflect the trauma patterns within the community, thus facilitating the development of a preventive strategy for the socioeconomic and environmental background of central Taiwan.

Fibrodysplasia ossificans progressiva: initial presentation with a preosseous lesion of the scalp and its MRI appearance.

This case subject is a 1-year-old girl presenting with recurrent diffuse soft-tissue swelling of the scalp and periorbital region. Her family denied any known history of trauma. There was no obvious discoloration or local heat at the lesion. Magnetic resonance imaging (MRI) revealed diffuse soft tissue swelling of the scalp manifesting as high signal intensity on T2-weighted images and low signal intensity on T1-weighted images with diffuse enhancement after gadolinium-contrast administration. Biopsy yielded inconclusive pathological results. Fibrodysplasia ossificans progressiva (FOP) was not suspected until malformation of the patient's toes was noticed. The scalp lesion underwent spontaneous regression, and subsequent radiographs of the chest and cervical spine revealed heterotopic ossifications of the neck and thorax. Early diagnosis of FOP is vital because trauma, unnecessary biopsy and intramuscular injection are known to cause acceleration of heterotopic ossifications. Previous studies reported diffuse soft tissue swelling at the posterior neck, thoracic wall or paraspinal region as preosseous lesions of FOP (Shiva Kumar et al. Neurology. 2010;74(6):e20, Merchant et al. Pediatr Radiol. 2006;36(10):1108-11, Hagiwara et al. AJR Am J Roentgenol. 2003;181(4):1145-7). To our knowledge, diffuse soft tissue swelling of the scalp as a preosseous lesion of FOP and associated MRI findings have not yet been reported. We believe that awareness of preosseous lesions presenting as diffuse soft tissue swelling, in addition to shortening and valgus deformity of the great toes, is an important diagnostic clue for establishing FOP.

Smad4 Deficiency in Smooth Muscle Cells Initiates the Formation of Aortic Aneurysm.

RATIONALE: Aortic aneurysm is a life-threatening cardiovascular disorder caused by the predisposition for dissection and rupture. Genetic studies have proved the involvement of the transforming growth factor-ß (TGF-ß) pathway in aortic aneurysm. Smad4 is the central mediator of the canonical TGF-ß signaling pathway. However, the exact role of Smad4 in smooth muscle cells (SMCs) leading to the pathogenesis of aortic aneurysms is largely unknown. OBJECTIVE: To determine the role of smooth muscle Smad4 in the pathogenesis of aortic aneurysms. METHODS AND RESULTS: Conditional gene knockout strategy combined with histology and expression analysis showed that Smad4 or TGF-ß receptor type II deficiency in SMCs led to the occurrence of aortic aneurysms along with an upregulation of cathepsin S and matrix metallopeptidase-12, which are proteases essential for elastin degradation. We further demonstrated a previously unknown downregulation of matrix metallopeptidase-12 by TGF-ß in the aortic SMCs, which is largely abrogated in the absence of Smad4. Chemotactic assay and pharmacologic treatment demonstrated that Smad4-deficient SMCs directly triggered aortic wall inflammation via the excessive production of chemokines to recruit macrophages. Monocyte/macrophage depletion or blocking selective chemokine axis largely abrogated the progression of aortic aneurysm caused by Smad4 deficiency in SMCs. CONCLUSIONS: The findings reveal that Smad4-dependent TGF-ß signaling in SMCs protects against aortic aneurysm formation and dissection. The data also suggest important implications for novel therapeutic strategies to limit the progression of the aneurysm resulting from TGF-ß signaling loss-of-function mutations.

SORLA-dependent and -independent functions for PACS1 in control of amyloidogenic processes.

Sorting-related receptor with A-type repeats (SORLA) is a sorting receptor for the amyloid precursor protein (APP) that prevents breakdown of APP into Aß peptides, a hallmark of Alzheimer's disease (AD). Several cytosolic adaptors have been shown to interact with the cytoplasmic domain of SORLA, thereby controlling intracellular routing of SORLA/APP complexes in cell lines. However, the relevance of adaptor-mediated sorting of SORLA for amyloidogenic processes in vivo remained unexplored. We focused on the interaction of SORLA with phosphofurin acidic cluster sorting protein 1 (PACS1), an adaptor that shuttles proteins between the trans-Golgi network (TGN) and endosomes. By studying PACS1 knockdown in neuronal cell lines and investigating transgenic mice expressing a PACS1-binding-defective mutant form of SORLA, we found that disruption of SORLA and PACS1 interaction results in the inability of SORLA/APP complexes to sort to the TGN in neurons and in increased APP processing in the brain. Loss of PACS1 also impairs the proper expression of the cation-independent mannose 6-phosphate receptor and its target cathepsin B, a protease that breaks down Aß. Thus, our data identified the importance of PACS1-dependent protein sorting for amyloidogenic-burden control via both SORLA-dependent and SORLA-independent mechanisms.