Impact of comorbidities on relapsing rates of Neuromyelitis Optica Spectrum Disorders: Insights from a longitudinal study in Taiwan.

BACKGROUND: Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune inflammatory demyelinating disease characterized by relapsing clinical episodes and the presence of autoantibodies. The impact of comorbidities on relapsing rate of NMOSD patients in Taiwan remains unclear. METHODS: We conducted a longitudinal retrospective study using the largest hospital system in Taiwan from 2006 to 2021. Demographic characteristics, annualized relapse rates (ARR), and comorbidities were examined. RESULTS: We identified 485 NMOSD patients from 2006 to 2021. Of these, 466 had the adult form and 19 (3.9 %) had the pediatric form of NMOSD. The median ARR was 0.51 (interquartile range (IQR): 0.26-1.11) for adults and 0.39 (IQR: 0.21-0.77) for pediatric patients. Comorbidities included malignancy (6.7 %) and autoimmune diseases (21.7 %). The recommended age for malignancy surveillance in NMOSD patients was 43.3 years. Neither malignancy nor autoimmune disease increased the ARR within 3 years post diagnosis in NMOSD patients with comorbidities compared with those without comorbidities. CONCLUSIONS: Our study revealed the ARR within the initial three years after diagnosis was significantly higher, emphasizing the importance of early treatment. We also observed an association between malignancy and NMOSD, and a significantly higher risk of malignancy in adult patients with NMOSD than in the general population (the relative risk was 5.99) that requiring further investigations into the underlying mechanisms. These findings contribute to a better understanding of NMOSD and its comorbidities in Taiwan.

Myasthenia gravis and independent risk factors for recurrent infection: a retrospective cohort study.

BACKGROUND: Approximately 10% to 20% of myasthenia gravis (MG) patients have experienced a myasthenic crisis (MC), which contributes to morbidity and mortality. MC triggered by infection is associated with poor outcomes. However, there is a lack of prognostic factors that clinicians can utilize to target interventions for preventing recurrent infection-triggered MC. This study aimed to characterize clinical manifestations, comorbidities, and biochemical profiles associated with recurrent infection-triggered MC in MG patients. METHODS: This retrospective study included 272 MG patients hospitalized with an infection requiring at least 3 days of antibiotics from January 2001 to December 2019. Patients were further stratified into non-recurrent or recurrent infection groups. Clinical features such as gender, age, concomitant diseases, acetylcholine receptor antibodies and biochemical data (including electrolytes and coagulants), muscle strength of pelvic and shoulder girdle, bulbar and respiratory function, management with an endotracheal tube, Foley catheter, or plasmapheresis, duration of hospitalization, and culture pathogens were recorded. RESULTS: The recurrent infection group was significantly older than the non-recurrent group (median age, 58.5 versus 52.0 years). Pneumonia was the most common infection and Klebsiella pneumoniae was the most common pathogen. The presence of concomitant diabetes mellitus, activated partial thromboplastin time prolongation, the duration of hospitalization, and hypomagnesaemia were independently associated with recurrent infection. The presence of deep vein thrombosis, thymic cancer, and electrolyte imbalances i.e., hypokalemia, and hypoalbuminemia were significantly associated with a risk for infection. The influence of endotracheal intubation, anemia, and plasmapheresis during hospitalization were inconsistent. CONCLUSIONS: The independent risk factors for recurrent infections in MG patients identified in this study include the presence of concomitant diabetes mellitus, hypomagnesaemia, activated partial thromboplastin time prolongation, and longer duration of hospitalization, highlighting the need for targeted interventions to prevent recurrent infections in this population. Further research and prospective studies are warranted to validate these findings and refine interventions for optimizing patient care.

The interaction of macrophages and CD8 T cells in bronchoalveolar lavage fluid is associated with latent tuberculosis infection.

Mycobacterium tuberculosis (Mtb) infection, including active tuberculosis (TB) and latent Mtb infection (LTBI), leads to diverse outcomes owing to different host immune responses. However, the immune mechanisms that govern the progression from LTBI to TB remain poorly defined in humans. Here, we profiled the lung immune cell populations within the bronchoalveolar lavage fluid (BALF) from patients with LTBI or TB using single-cell RNA sequencing (scRNA-seq). We found that Mtb infection substantially changed the immune cell compartments in the BALF, especially for the three subsets of macrophages, monocyte macrophage (MM)-CCL23, MM-FCN1, and MM-SPP1, which were found to be associated with the disease status of TB infection. Notably, MM-CCL23 cells derived from monocytes after stimulation with Mtb were characterized by high levels of chemokine (CCL23 and CXCL5) production and might serve as a marker for Mtb infection. The MM-CCL23 population mainly recruited CD8-CCR6 T cells through CCL20/CCR6, which was a prominent feature associated with protection immunity in LTBI. This study improves our understanding of the lung immune landscape during Mtb infection, which may inform future vaccine design for protective immunity.

The analysis of cathepsin L that mediates cellular SARS-CoV-2 infection leading to COVID-19 in head and neck squamous cell carcinoma.

The vulnerability of the oral cavity to SARS-CoV-2 infection is well-known, and cancer patients are at a higher risk of COVID-19, emphasizing the need to prioritize this patient population. Head and neck squamous cell carcinoma (HNSCC) is one of the most common malignant cancers associated with early metastasis and poor prognosis. It has been established that cancerous tissues express Cathepsin L (CTSL), a proteinase that regulates cancer progression and SARS-CoV-2 entry. Therefore, it is essential to evaluate the correlation between disease outcomes and CTSL expression in cancer tissues and predict the susceptibility of cancer patients to SARS-CoV-2. In this study, we used transcriptomic and genomic data to profile CTSL expression in HNSCC and developed a CTSL signature that could reflect the response of HNSCC patients to chemotherapy and immunotherapy. Additionally, we investigated the relationship between CTSL expression and immune cell infiltration and established CTSL as a potential carcinogenic factor for HNSCC patients. These findings could aid in understanding the mechanisms underlying the increased susceptibility of HNSCC patients to SARS-CoV-2 and contribute to the development of therapy for both HNSCC and COVID-19.

Uniportal versus triportal video-assisted thoracic surgery in the treatment of tuberculous empyema.

OBJECTIVE: To examine the effectiveness of decortication to treat chronic tuberculous empyema (TE) using uniport video-assisted thoracoscopic surgery (VATS) versus conventional triport VATS. METHODS: Data from consecutive patients with stage II or III TE who underwent decortication with either uniport VATS (uniportal group) between July and December 2017, or triport VATS between January and July 2018 (triportal group), were retrospectively analysed. VATS procedures were performed under general anaesthesia with double lumen endotracheal intubation and clinical outcomes were compared between the two groups. RESULTS: Clinical data were comparable between the groups (20 patients in each) regarding demographic and baseline characteristics, operative and postoperative characteristics, surgical procedure-related complications, and postoperative adverse events. No surgical procedure-related complications occurred during the perioperative period in either group. Threshold values for mechanical pain at 8 h postoperatively were significantly higher in the triportal group versus the uniportal group. Furthermore, the incidence of nausea and vomiting was significantly lower in the uniportal versus triportal group. In the triportal group, one patient required readmission and further intervention due to recurrence. CONCLUSIONS: Uniport VATS decortication for stages II and III TE may be a feasible and safe procedure in selected patients. Moreover, uniport VATS may be less painful than triport VATS.

Obesity Is Associated with Attenuated Tissue Immunity in COVID-19.

Rationale: Obesity affects 40% of U.S. adults, is associated with a proinflammatory state, and presents a significant risk factor for the development of severe coronavirus disease (COVID-19). To date, there is limited information on how obesity might affect immune cell responses in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Objectives: To determine the impact of obesity on respiratory tract immunity in COVID-19 across the human lifespan. Methods: We analyzed single-cell transcriptomes from BAL in three ventilated adult cohorts with (n = 24) or without (n = 9) COVID-19 from nasal immune cells in children with (n = 14) or without (n = 19) COVID-19, and from peripheral blood mononuclear cells in an independent adult COVID-19 cohort (n = 42), comparing obese and nonobese subjects. Measurements and Main Results: Surprisingly, we found that obese adult subjects had attenuated lung immune or inflammatory responses in SARS-CoV-2 infection, with decreased expression of IFN-α, IFN-γ, and TNF-α (tumor necrosis factor α) response gene signatures in almost all lung epithelial and immune cell subsets, and lower expression of IFNG and TNF in specific lung immune cells. Peripheral blood immune cells in an independent adult cohort showed a similar but less marked reduction in type-I IFN and IFNγ response genes, as well as decreased serum IFNα, in obese patients with SARS-CoV-2. Nasal immune cells from obese children with COVID-19 also showed reduced enrichment of IFN-α and IFN-γ response genes. Conclusions: These findings show blunted tissue immune responses in obese patients with COVID-19, with implications for treatment stratification, supporting the specific application of inhaled recombinant type-I IFNs in this vulnerable subset.

The correlation of small fiber neuropathy with pain intensity and age in patients with Fabry's disease: A cross sectional study within a large Taiwanese family.

BACKGROUND: The relationships among small fiber neuropathy, age, sex and pain intensity in the context of Fabry's disease remain unclear. We aim to study the correlations of small fiber neuropathy, age, sex and pain intensity in Fabry patients. METHODS: We evaluated C-fiber function by recording the withdrawal latencies to painful heat stimulus (WLPHS) when each subject's right hand was immersed in a 50 °C hot water bath and correlated this parameter with the patient's perceived pain intensity and quality of life assessed by the short-form McGill Pain Questionnaire (SF-MPQ) in a large Taiwanese Fabry family and normal controls. RESULTS: Male Fabry patients showed a significantly increased WLPHS compared to that of normal controls. Furthermore, male Fabry patients showed a positive correlation of increased WLPHS with patient age. The SF-MPQ of male Fabry patients showed a bell distribution with age, and maximal pain scores were detected between the ages of the early 20s and late 40s. In contrast, the female Fabry patients had variable associations of WLPHS and SF-MPQ with age. CONCLUSIONS: We proposed a probable mechanism by which globotriaosylceramide (Gb3) or globotriaosylsphingosine (lyso-Gb3) is gradually deposited into the small nerve bundles with increasing age, which induces continuous damage and produces injury discharges to sustain neuropathic pain in young male Fabry patients. However, once the small fibers are reduced to a certain degree, they no longer produce enough noxious discharges to sustain neuropathic pains in older male Fabry patients, which leads these patients to have lower SF-MPQ scores. In contrast, female Fabry patients had less and variable small fiber damage, pain intensity and clinical signs/symptoms.

Isaacs' syndrome as the initial presentation of malignant thymoma and associated with double-positive voltage-gated potassium channel complex antibodies, a case report.

BACKGROUND: Isaacs' syndrome is a peripheral nerve hyperexcitability (PNH) syndrome due to peripheral motor nerve instability. Acquired Isaacs' syndrome is recognized as a paraneoplastic autoimmune disease with possible pathogenic voltage-gated potassium channel (VGKC) complex antibodies. However, the longitudinal correlation between clinical symptoms, VGKC antibodies level, and drug response is still unclear. CASE PRESENTATION: A 45-year-old man had progressive four limbs soreness, muscle twitching, cramps, and pain 4 months before admission. Electromyography (EMG) studies showed myokymic discharges, neuromyotonia, and an incremental response in the high-rate (50 Hz) repetitive nerve stimulation (RNS) test. Isaacs' syndrome was diagnosed based on clinical presentations and EMG reports. Serum studies showed positive VGKC complex antibodies, including leucine-rich glioma-inactivated 1 (LGI1) and contactin-associated protein-like 2 (CASPR2) antibodies. The acetylcholine receptor antibody was negative. Whole-body computed tomography (CT) and positron emission tomography revealed a mediastinal tumor with the great vessels encasement, right pleura, and diaphragm seeding. Biopsy confirmed a World Health Organization type B2 thymoma, with Masaoka stage IVa. His symptoms gradually improved and both LGI1 and CASPR2 antibodies titer became undetectable after concurrent chemoradiotherapy (CCRT) and high dose steroid treatment. However, his Isaacs' syndrome recurred after the steroid was reduced 5 months later. Follow-up chest CT showed probable thymoma progression. LGI1 antibody turned positive again while CASPR2 antibody remained undetectable. CONCLUSIONS: Our patient demonstrates that Isaacs' syndrome could be the initial and only neuromuscular manifestation of malignant thymoma. His Isaacs' syndrome is correlated well with the LGI1 antibody level. With an unresectable thymoma, long-term immunosuppressant therapy may be necessary for the management of Isaacs' syndrome in addition to CCRT for thymoma.

Reappraisal of the incidence, various types and risk factors of malignancies in patients with dermatomyositis and polymyositis in Taiwan.

Our study aimed to investigate the incidence, risk factors and time to occurrence of malignancy in patients with dermatomyositis (DM) and polymyositis (PM). The electronic medical records of 1100 patients with DM and 1164 patients with PM were studied between January 2001 and May 2019. Malignancies after myositis were diagnosed in 61 (5.55%) patients with DM and 38 (3.26%) patients with PM. The cumulative incidence of malignancies in patients with DM were significantly higher than patients with PM (hazard ratio = 1.78, log-rank p = 0.004). Patients with DM had a greater risk of developing malignancy than those with PM at 40-59 years old (p = 0.01). Most malignancies occurred within 1 year after the initial diagnosis of DM (n = 35; 57.38%). Nasopharyngeal cancer (NPC) was the most common type of malignancy in patients with DM (22.95%), followed by lung, and breast cancers. In patients with PM, colorectal, lung and hepatic malignancies were the top three types of malignancy. The risk factors for malignancy included old age (≥ 45 years old) and low serum levels of creatine phosphokinase (CPK) for patients with DM and male sex and low serum levels of CPK for patients with PM. Low serum levels of CPK in patients with myositis with malignancy represented a low degree of muscle destruction/inflammation, which might be attributed to activation of the PD-L1 pathway by tumor cells, thus inducing T-cell dysfunction mediating immune responses in myofibers. A treatment and follow-up algorithm should explore the occurrence of malignancy in different tissues and organs and suggested annual follow-ups for at least 5.5 years to cover the 80% cumulative incidence of malignancy in patients with DM and PM.

Granulocyte Colony Stimulating Factor (GCSF) Can Attenuate Neuropathic Pain by Suppressing Monocyte Chemoattractant Protein-1 (MCP-1) Expression, through Upregulating the Early MicroRNA-122 Expression in the Dorsal Root Ganglia.

Our previous animal studies and several human clinical trials have shown that granulocyte-colony stimulating factor (GCSF) can attenuate neuropathic pain through various mechanisms. GCSF itself is also a multipotent cytokine that can modulate microribonucleic acid (microRNA) expression profiles in vitro. In this study, we used the NanoString nCounter analysis system to screen the expression of different rodent microRNAs at early stage after nerve injury and studied the expression of related cytokines/chemokines in the dorsal root ganglia (DRGs) of rats that underwent chronic constriction injury (CCI) to explore the underlying mechanisms of the analgesic effects of GCSF. We found that microRNA-122 expression was downregulated by CCI; in contrast, GCSF treatment significantly upregulated microRNA-122 expression in the DRGs of CCI rats on the 1st day after nerve injury. We further studied the expression of different cytokines/chemokines (IL-1ß, IL-6, and monocyte chemoattractant protein-1 (MCP-1)) that were modulated by microRNA-122. MCP-1 has been reported to participate in neuropathic pain development, and its expression on the DRGs of vehicle-treated CCI rats was significantly higher than that on the DRGs of sham-operated rats; in contrast, GCSF-treated rats exhibited significantly lower MCP-1 expression in the DRG than vehicle-treated rats on the 7th day after nerve injury. An early GCSF treatment can suppress MCP-1 expressions, through upregulating microRNA-122 expressions in the DRGs of CCI rats at an earlier stage, thus indirectly attenuating neuropathic pain development.

Uniportal Thoracoscopic Wedge Resection of Lung Nodules: Paravertebral Blocks Are Better Than Intercostal Blocks.

Background. Regional analgesia for tubeless, uniport, thoracoscopic wedge resection of benign peripheral nodules is generally performed by intercostal nerve block (INB). We examined the effectiveness of thoracic paravertebral block (PVB), in comparison to the traditional intercostal blocks, for the procedure. Methods. Between July 2016 and December 2016, 20 consecutive patients with solitary benign peripheral lung nodules underwent tubeless uniport thoracoscopic wedge resection using thoracic PVB (PVB group). The clinical outcomes were compared with those of 20 other consecutive patients who underwent the same procedure under the conventional INB, between January 2016 and July 2016 (INB group). In both groups, the procedures were performed without endotracheal intubation, urinary catheterization, or chest tube drainage. Results. The clinical data of patients in both groups were comparable in terms of demographic and baseline characteristics, operative and anesthetic characteristics, puncture-related complications, and postoperative anesthetic adverse events. No puncture-related complications occurred during the perioperative period in either group. The threshold values for mechanical pain at postoperative hours 4 and 8 were significantly higher in the PVB group than in the INB group. Furthermore, the incidence of nausea or vomiting in the PVB group was significantly less than that in the INB group. None of the patients required reintervention or readmission to our hospital. Conclusions. Tubeless uniportal thoracoscopic wedge resection for solitary benign peripheral lung nodules using thoracic PVB for regional analgesia is a feasible and safe procedure. Moreover, we found that thoracic PVB is less painful than INB.

Early enteral feeding on esophageal cancer patients after esophageal resection and reconstruction.

BACKGROUND: In patients under esophagectomy, early postoperative oral feeding has traditionally been contraindicated to minimize the risk of anastomotic leaks. Because early oral feeding preserves the integrity and function of gut mucosa, the aim of this study was to investigate the impact of postoperative early oral feeding on esophagectomy. METHODS: Between Oct 2013 and Jan 2016, 41 consecutive patients with esophageal carcinoma (stages I- III), who had undergone minimally invasive Ivor-Lewis surgery, were enrolled in this study. The patients were randomly arranged into the early oral feeding (EOF) group (21 cases) and the simple tube feeding (STF) group (20 cases). The nutritional goal for both groups was 25 kcal/(kg·day). The patients in the EOF group were tube-fed with enteral nutrition and orally fed with 5% glucose in normal saline during the first 4 postoperative days, after that the patients were placed on a liquid diet. The patients in the STF group were postoperatively tube-fed with enteral nutrition for 7 days before being switched to liquid diet. The length of the postoperative hospital stay, rate of perioperative complications, and overall mortality were recorded. Preoperative and postoperative levels of serum albumin (ALB), prealbumin (PA), transferrin (TP), and C reactive protein (CRP) were also monitored. RESULTS: There were no significant differences of the incidence of postoperative complications and overall mortality between the EOF group and the STF group, but the duration of hospital stay, interval until the first liquid food, and time of ambulation in the EOF group were lower than those of the STF group (P<0.05). EOF patients also showed significantly lower CRP levels compared with the STF group (P<0.05). CONCLUSIONS: EOF might reduce the duration of hospital stays and CRP levels in esophageal cancer patients who underwent esophagectomy while the mortality and complications were not affected.

CD157 Confers Host Resistance to Mycobacterium tuberculosis via TLR2-CD157-PKCzeta-Induced Reactive Oxygen Species Production.

Recruitment of monocytes to the infection site is critical for host resistance against Mycobacterium tuberculosis CD157 has a crucial role in neutrophil and monocyte transendothelial migration and adhesion, but its role in tuberculosis (TB) is unclear. Here, we show that both mRNA and protein levels of Cd157 are significantly increased during M. tuberculosis infection. Deficiency of Cd157 impaired host response to M. tuberculosis infection by increasing bacterial burden and inflammation in the lung in the murine TB model. In vitro experiments show that the bactericidal ability was compromised in Cd157 knockout (KO) macrophages, which was due to impaired M. tuberculosis-induced reactive oxygen species (ROS) production. We further reveal that CD157 interacts with TLR2 and PKCzeta and facilitates M. tuberculosis-induced ROS production in Cd157 KO macrophages, which resulted in enhanced M. tuberculosis killing. For the clinic aspect, we observe that the expression of CD157 decreases after effective anti-TB chemotherapy. CD157 is specifically increased in pleural fluid in tuberculous pleurisy patients compared to pneumonia and lung cancer patients. Interestingly, the levels of soluble CD157 (sCD157) correlate with human peripheral monocyte-derived macrophage bactericidal activity. Exogenous application of sCD157 could compensate for macrophage bactericidal ability and restore ROS production. In conclusion, we have identified a novel protective immune function of CD157 during M. tuberculosis infection via TLR2-dependent ROS production. Application of sCD157 might be an effective strategy for host-directed therapy against TB in those with insufficient CD157 production.IMPORTANCE Tuberculosis, a chronic bacterial disease caused by Mycobacterium tuberculosis, remains a major global health problem. CD157, a dual-function receptor and ß-NAD+-metabolizing ectoenzyme, promotes cell polarization, regulates chemotaxis induced through the high-affinity fMLP receptor, and controls transendothelial migration. The role of CD157 in TB pathogenesis remains unknown. In this study, we find that both mRNA and protein levels of CD157 are significantly increased in TB. Deficiency of CD157 impaired host defense against M. tuberculosis infection both in vivo and in vitro, which is mediated by an interaction among CD157, TLR2, and PKCzeta. This interaction facilitates M. tuberculosis-induced macrophagic ROS production, which enhances macrophage bactericidal activity. Interestingly, the sCD157 level in plasma is reversibly associated with MDM M. tuberculosis killing activity. By uncovering the role of CD157 in pathogenesis of TB for the first time, our work demonstrated that application of soluble CD157 might be an effective strategy for host-directed therapy against TB.

A comparison between spinal cord infarction and neuromyelitis optica spectrum disorders: Clinical and MRI studies.

This study aims to investigate the clinical features and magnetic resonance imaging (MRI) findings in patients with spinal cord infarction (SCI) and neuromyelitis optica spectrum disorders (NMOSDs). Over a period of 16 years, we retrospectively analyzed 39 patients with SCI and 21 patients with NMOSD. The demographic features and clinical presentations of both diseases were carefully documented. Etiology-specific MRI features, such as the length and distribution of the lesions, the owl's eyes sign and bright spotty lesions, were recorded and analyzed regarding their association with the clinical signs/symptoms. Patients with SCI were older than patients with NMOSD and had sudden onset of clinical symptoms with focal pain adjacent to the lesions. Concomitant spinal cord and vertebral body infarctions were frequently associated with aortic pathology (p = 0.04). In addition, artery dissection was highly associated with combined ASA and unilateral PSA infarctions and long segments of SCI (all p < 0.05). In contrast, patients with NMOSD had a relatively younger age of onset, female predominance and subacute progression of limbs weakness. As observed by MRI, the length and location of the lesions demonstrated significant differences between the two diseases (P < 0.01). The owl's eyes sign showed more frequently in patients with SCI than NMOSD (p < 0.01). The predicted prognoses in SCI and NMOSD were significantly associated with initial motor function (muscle power), after adjustments for age and gender (p < 0.01 and p = 0.02, respectively). Along with patient demographic characteristics, lesion features on MRI can help clinicians differentiate acute noncompressive myelopathy due to SCI from that due to NMOSD, which may lead to immediate initiation of adequate therapeutic measures.

Genetic Analysis of Hereditary Transthyretin Ala97Ser Related Amyloidosis.

Genetic testing is the most reliable test for hereditary transthyretin related amyloidosis and should be performed in most cases of transthyretin amyloidosis (ATTR). ATTR is a rare but fatal disease with heterogeneous phenotypes; therefore, the diagnosis is sometimes delayed. With increasing attention and broader recognition on early manifestations of ATTR as well as emerging treatments, appropriate diagnostic studies, including the transthyretin (TTR) genetic test, to confirm the types and variants of ATTR are therefore fundamental to improve the prognosis. Genetic analyses with polymerase chain reaction (PCR) methods confirm the presence of TTR point mutations much more quickly and safer than conventional methods such as southern blot. Herein, we demonstrate genetic confirmation of the ATTR Ala97Ser mutation, the most common endemic mutation in Taiwan. The protocol comprises four main steps: collecting whole blood specimen, DNA extraction, genetic analysis of all four TTR exons with PCR, and DNA sequencing.

A prospective, observational study of patients with uncommon distal symmetric painful small-fiber neuropathy.

OBJECTIVE: To investigate the clinical characteristics of patients with uncommon distal symmetric painful small-fiber neuropathy (DSPSFN). METHODS: From September 2012 to September 2014, participants between 18-70 years of age that had DSPSFN defined by clinical signs/symptoms and ID pain > 2 or DN4 > 4 on questionnaires for more than 1 month were included. Participants who had previous historical or laboratory evidence of common etiologies of DSPSFN were excluded. Enzyme activity and genetic studies for Fabry diseaseand familial amyloid polyneuropathy were performed after participants fulfilled the inclusion and exclusion criteria. The cryoglobulin test, autoantibodies studies and electrophysiological studies were performed in these participants. RESULTS: In total, 100 cases were enrolled in the current study. Three cases of subclinical diabetes mellitus and two cases of fibromyalgia were found. Fabry disease (1%) and familial amyloid polyneuropathy (3%) with Ala97Ser transthyretin (TTR) mutations were also detected. The cryoglobulin test was positive in 30% of participants, and these participants had higher DN4 scores than the negative group. In the autoantibodies studies, 59% of the participants had abnormal anti-Ro/SSA and/or anti-La/SSB antibodies. CONCLUSIONS: Cryoglobulinemia is not a rare etiology of uncommon DSPSFN. The long-term prognosis is quite good in these participants. From our structuralized protocol, Fabry disease and familial amyloid polyneuropathy could be easily detected in these cases of uncommon DSPSFN.

Phenotypic expressions of hereditary Transthyretin Ala97Ser related Amyloidosis (ATTR) in Taiwanese.

BACKGROUND: The disease course and early signs specific to ATTR Ala97Ser, the most common endemic mutation in Taiwan, have not been well described. Since new medications can slow down the rate of disease progression, the early diagnosis of this heterogeneous and fatal disease becomes critical. METHODS: We retrospectively reviewed the characteristics of genetically confirmed ATTR Ala97Ser patients at a tertiary referral medical center. RESULTS: Eight patients from 7 different families were enrolled (61.7 ± 5.5 years). Gastrointestinal symptoms, dyspnea or chest tightness, rather than sensory symptoms, were the initial symptoms in two patients (2/7 = 29%). Body weight loss (3/7 = 43%), muscle wasting (4/7 = 57%), or dysphagia (3/7 = 43%) were the consecutive symptoms. Orthostatic symptoms including orthostatic hypotension (7/7 = 100%), dizziness (6/7 = 86%) and syncope (5/7 = 71%) tended to develop in the late phase of the disease. Autonomic dysfunction was conspicuous. Cardiographic findings included a combination of ventricular wall thickening and pericardial effusion (7/7 = 100%), a granular sparkling appearance of the ventricular myocardium (4/7 = 57%), or conduction abnormalities (5/7 = 71%). CONCLUSIONS: This study broadens the recognition of the initial signs and symptoms, including cardiographic findings and longitudinal manifestations in Taiwanese individuals with ATTR Ala97Ser mutation. These manifestations should prompt doctors to perform further studies and make an early diagnosis.

McGrath Series 5 videolaryngoscope vs Airtraq DL videolaryngoscope for double-lumen tube intubation: A randomized trial.

BACKGROUND: Many studies have shown Airtraq videolaryngoscope provided faster tracheal intubation and a higher success rate than other videolaryngoscopes. Recently, different types of videolaryngoscopes have been reported for use in double-lumen tube (DLT) intubation. However, the advantages and disadvantages between them remain undetermined for DLT intubation. In this study, we compared the Airtraq DL videolaryngoscope with the McGrath Series 5 videolaryngoscope for DLT intubation by experienced anesthesiologists. METHODS: Ninety patients with expected normal airways were randomly allocated to either the Airtraq or McGrath group. The primary outcome was DLT intubation time. The secondary outcomes were glottic view, success rate, subjective ease of intubation (100-mm visual analog scale, 0 = easy; 100 = difficult), incidence of DLT malposition, and postoperative intubation-related complication. RESULTS: The airway characteristics were comparable between the 2 groups. Cormack and Lehane grades significantly improved with the use of the McGrath and Airtraq videolaryngoscopes, compared with the Macintosh laryngoscope. The intubation success rate on the first attempt was 93% in the Airtraq group and 95% in the McGrath group (P > 0.05). The intubation time in the McGrath group is longer than that in the Airtraq group (39.9 [9.1]s vs 28.6 [13.6]s, P < 0.05). But intubation difficulty score, the incidence of DLT malposition and intubation-related complication were comparable between groups (P > 0.05). CONCLUSIONS: When using videolaryngoscopes for DLT intubation, the Airtraq DL is superior to the McGrath Series 5 in intubation time, but it does not decrease intubation difficulty.

Down-regulation of miR-20a-5p triggers cell apoptosis to facilitate mycobacterial clearance through targeting JNK2 in human macrophages.

Induction of cell apoptosis is one of the major host defense mechanisms through which macrophages control Mycobacterium tuberculosis (Mtb) infection. However, the mechanisms underlying macrophage apoptosis triggered by Mtb infection are still largely unknown. In this study, a microarray profiling survey revealed 14 miRNAs were down-regulated in CD14+ monocytes from active pulmonary tuberculosis patients, and only the reduction of miR-20a-5p could be reversed after successful anti-tuberculosis treatment. Validation of miR-20a-5p expression was confirmed using real time qPCR. Moreover, miR-20a-5p expression also decreased in differentiated THP-1 macrophages after mycobacterial infection in vitro. Functional assays through forced or inhibited expression of miR-20a-5p in THP-1 macrophages demonstrated that miR-20a-5p functioned as a negative regulator of mycobacterial-triggered apoptosis. Importantly, inhibition of miR-20a-5p expression resulted in more efficient mycobacterial clearance from infected THP-1 macrophages while miR-20a-5p overexpression promoted mycobacterial survival. Mechanistically, miR-20a-5p was demonstrated to regulate Bim expression in a JNK2-dependent manner, unlike Bcl2, and luciferase assay showed JNK2 was a novel direct target of miR-20a-5p. Together, our findings indicate that downregulation of miR-20a-5p triggers macrophage apoptosis as a novel mechanism for host defense against mycobacterial infection.

xCT increases tuberculosis susceptibility by regulating antimicrobial function and inflammation.

The physiological functions of macrophage, which plays a central role in the pathogenesis of tuberculosis, depend on its redox state. System xc-, a cystine-glutamate transporter, which consists of xCT and CD98, influences many ROS-dependent pathways by regulating the production of the antioxidant glutathione. xCT's ability to alter this critical host redox balance by increasing the glutathione synthesis aspect of phagocyte physiology suggested that it might influence tuberculosis pathogenesis. In this study, we found that the xCT expression was increased in peripheral blood monocyte of active tuberculosis. xCT expression in macrophage was induced by Mycobacterium tuberculosis (Mtb) through TLR2/Akt- and p38-dependent signaling pathway. Importantly, xCT deficiency conferred protection against tuberculosis, as xCT knock out mice displayed increased Mtb load and reduced pulmonary pathology in lung compared to wild type mice. xCT disruption enhanced the mycobateriacidal activity of macrophage through increasing the mycothiol oxidation. Importantly, chemical inhibition of xCT with sulfasalazine, a specific xCT inhibitor that is already approved by the FDA for treatment of inflammatory bowel disease, produces similar protective effects in vivo and in vitro, indicating xCT might be a novel and useful target for host-directed TB treatment strategy.