Pneumatosis Cystoides Intestinalis Complicated during Chemotherapy for Pulmonary Nontuberculous Mycobacterial Disease

Background: Pneumatosis cystoides intestinalis (PCI) is a rare disease characterized by the presence of gas in the intestinal wall. Aim: We report two rare cases of PCI that are complicated during the chemotherapy for pulmonary nontuberculous mycobacterial (NTM) disease. Case Presentation: In this report, we described two cases (a 72-year-old woman and a 60-year-old woman) of PCI that appeared during the combined chemotherapy consisting of rifampicin, ethambutol and clarithromycin. Because there were few clinical symptoms and increased inflammatory responses, the diagnosis of PCI was delayed. However, there were fortunately no severe complications in both cases. Conclusion: Respiratory physicians should be aware of the potential development of PCI in patients during the chemotherapy for pulmonary NTM disease. It is important to detect PCI in the early stage through radiological examinations to avoid severe complications.

A Retrospective Study of Culture-confirmed Mycobacterial Infection among Hospitalized HIV-infected Patients in Beijing, China

A retrospective analysis was performed in two major HIV/AIDS referral hospitals in Beijing to evaluate the prevalence of Mycobacterium tuberculosis（MTB） and non-tuberculous mycobacterial（NTM） infections in HIV-infected patients. A total of 627 patients＇ data were reviewed, and 102（16.3%） patients were diagnosed with culture-confirmed mycobacterial infection, including 84 with MTB, 16 with NTM, and 2 with both MTB and NTM. The most frequent clinical complication by mycobacterial infection was pulmonary infection（48/102, 47.1%）. The overall rates of multidrug-resistant TB（MDR-TB） and extensively drug-resistant TB（XDR-TB） were 11.9% and 3.4%, respectively. This study underlines the urgent need to intensify screening for mycobacteria coinfection with HIV and to prevent the spread of drug-resistant TB among HIV-infected patients.

Cervical Nontuberculous Mycobacterial Lymphadenitis Mimicking a Thyroid Tumor and Infiltrating Deep into the Neck

Aim: Nontuberculous Mycobacterial Lymphadenitis (NML), which occurs in 1.2 per 100,000 children, is very rare. And those which emerge at the anterior cervical portion and infiltrate deep into the neck are even more rare. Generally, this disorder is uncommon existed near the thyroid gland. We report here a case of NML mimicking a thyroid tumor and infiltrating into the deep part of the anterior neck. Case: A mass at the anterior portion of her neck was found at 5 years old. It was not mobile and palpated as an irregularly surfaced hard mass whose size was 3 cm at the anterior lower portion of her neck. Ultrasonography showed an oval mass which existed near the slightly inferior part of the right lobe of the thyroid gland. Enhanced computed tomography showed a mass near the slightly inferior part of the right lobe of the thyroid gland. The mass was resected with the platysma and the right sternohyoid muscle. In the HE staining, epithelioid cell and Langhans type giant cells surrounding coagulative necrosis lesions which seemed to be caseation necrosis existed, similarly to cervical NML. Discussion: No consensus exists for the treatment of NML, but many documents advise complete excision. When the lesion cannot be completely removed, excision as far as possible and additional antibiotics are recommended. The characteristics of imaging of NML around the thyroid gland and infiltrating deep into the anterior neck and mediastinum are discussed.

Insights on Blood Cytokines Production under Different <i>In Vitro</i>Mycobacterial Antigens in Tuberculosis Intestinal Parasites Co Infected Patients

Background: The concomitant presence of intestinal parasite infections (IP) and tuberculosis (TB) has relevance. M. tuberculosis immune response is associated with type 1 T helper cell (Th1) while IP is associated with type Th2 cell. However, there are several contradictory reports on cytokine production under coinfection and this could be in association to the mycobacterial antigens used in the studies. Aim: To get insight into the effects of different M. tuberculosis-specific antigens (ESAT-6/CFP-10 and 38 kDa/CFP-10) in generating of appropriate cytokines on peripheral blood mononuclear cells of IPTB co infected patients. Method: ELISA assessed IFN-γ and other 16 cytokines production and plasm IgE. In 18 months, we documented demographic, economic, clinical characteristics and IP frequency in individuals from Brazil. Results: An overall 10/35 (28.5%) were IPTB co infected and 40/76 (52.6%;p = 0.024) asymptomatic intestinal parasite infected community controls (IPCC). Endo-limax nana (40%) and Entamoeba coli (22%), were the most nonpathogenic protozoan identified and Entamoeba histolytica, Giardia intestinalis, Ascaris lumbricoides and Strongyloides stercoralis were the pathogenic species (40%). IgE was higher in IPCC (p = 0.036). Cytokine profiles were significantly biased toward a Th2 type IL-5 (p = 0.001) and IL-13 (p = 0.033), pro-inflammatory GM-CSF (p = 0.019) and borderline lower IL-1β in IPTB, all associated with ESAT-6/CFP-10, while IL-7 was borderline lower, but 38 kDa/CFP-10 associated;as well as IL-8 higher (p < 0.049) vs CC/IPCC. The TB/IPTB IFN-γ levels were similar to both antigens stimuli (p ≥ 0.208). Conclusion: Therefore, coin-cident IPTB coinfection did not exert a significant inhibitory effect in IFN-γ production in response to either of the two antigens, but the partial discrepancy in Th1/Th2 response, is associated with the antigen priming cells.

Clinical Analysis of Pulmonary Nontuberculous Mycobacterial Disease Complicated by Lung Cancer during the Follow-Up Periods

Introduction: The objective of this study was the estimation of the clinical characteristics of patients with pulmonary nontuberculous mycobacterial (NTM) disease complicated by lung cancer during the follow-up periods. Methods: We analyzed the clinical findings of four patients (2.0%) complicated by lung cancer during the follow-up periods of over six months at least after the definite diagnosis of pulmonary NTM disease of 202 patients with pulmonary NTM disease experienced in our hospital in the last decade. Results: There were four patients with pulmonary NTM disease complicated by lung cancer and all of them were caused by Mycobacterium avium complex (MAC). They were all elderly male patients and had underlying diseases. Three patients were diagnosed with primary lung cancer and one diagnosed with metastatic lung cancer from colon cancer within 3 years after the diagnosis of pulmonary NTM disease. The treatments for lung cancer were surgical resection for all patients with localized lesions. One patient died due to the worsening of underlying disease and the remaining three survived except for the recurrence of one patient. Conclusion: Although the complication rate of pulmonary NTM disease and lung cancer was a lower percentage (2.0%) than in previous reports, the careful follow-up for patients with pulmonary NTM disease without forgetting the possible complication of lung cancer is necessary.

Late recurrence in surgically managed pediatric atypical mycobacterial lymphadenitis:A case report and review of the literature

Objective:The purpose of this study is to identify existing literature on recurrent atypical mycobacterial cervicofacial lymphadenitis to augment our understanding of a unique patient who presented to our tertiary‐care center 5‐years posttreatment with recurrence following curettage.Data Sources:OVID Medline,Scopus,and Web of Science.Methods:A literature search was conducted yielding 49 original articles which were screened twice by two independent reviewers resulting in 14 studies meeting inclusion criteria for data extraction using Covidence software.Two independent reviewers extracted data on recurrence of atypical mycobacterial cervicofacial lymphadenitis and consensus was reached on data points from all included studies.Results:This study illuminated the paucity of recurrence reporting in the literature regarding atypical mycobacterial lymphadenitis.Sixteen studies identified in our review included discussions on recurrence with few elaborating beyond the rate of recurrence to describe their management.Fourteen out of sixteen studies provided recurrence rates for their cohort,11 out of 14 specified the initial treatment modality,and only five out of eight studies that described initial treatment with surgery differentiated recurrence rates between complete and incomplete excision.The mean length of follow‐up in the included studies was 20 months.There was one previously reported case of late recurrence at 5‐years.Conclusions:We identified few reports that discussed the management of recurrence of atypical mycobacterial cervicofacial lymphadenitis.There was minimal data on recurrence rates between surgical treatment modalities.The case discussed in our study showcases that treatment with curettage has the potential to present with late recurrence.

Insights on the crosstalk between dendritic cells and helper T cells in novel genetic etiology for mendelian susceptible mycobacterial disease

Mendelian susceptibility to mycobacterial disease(MSMD)is an inherited predisposition to infections by Bacille-Calmette Guérin(BCG)vaccine or by environmental mycobacteria.The etiology of MSMD has been associated with up to nineteen different genetic mutations in interferon(IFN)-γ-related genes.1 Although mycobacteria susceptibility-associated genetic mutations are rare in the population,their diagnosis is crucial for an efficient and timely treatment.Kong et al.2 have recently described an autosomal recessive deficiency in the signal peptidase-like 2 A(SPPL2-a)as a new genetic etiology for MSMD in three patients that had suffered BCG dissemination disease.

A Systematic Review on Antituberculosis Drug Discovery and Antimycobacterial Potential of Biologically Synthesized Silver Nanoparticles:Overview and Future Perspectives

Rapid emergence and quick evolution of drug-resistant and aggressive mycobacterial strains have resulted in the present antimycobacterial drug crisis and the persistence of tuberculosis as a major public health problem.Green/biological nanotechnologies constitute an interesting area of research for discovering antimycobacterial agents.This review focused on the biological(green)synthesis of silver nanoparticles(AgNPs)as an alternative source of antimycobacterial agents.Data for this study were searched and screened from three electronic databases(Google Scholar,PubMed and ScienceDirect)following the Preferred Reporting Items for Systematic Reviews and Meta-analyses flowchart.Data from in total 17 eligible studieswere reported in this systematic review.Twelve of the 17 studies used plants to fabricate AgNPs,whereas the remaining five studies used microorganisms(bacteria and/or fungi).Silver as part of silver nitrate(AgNO3)was themetal precursor reported for the synthesis of AgNPs in these studies.Silver nanoparticles were mostly spherical,with sizes ranging from12 to140nm.Resultsbasedon minimum inhibitory concentrations varied between studies and were divided into three groups:(i)those more effective than the antibiotic(controls),(ii)those more effective than plant extracts,and(iii)those less effective than the antibiotic controls.In addition,little or no cytotoxicity effects were reported.Silver nanoparticles were also shown to be highly specific or selective toward mycobacterial strains.This systematic review highlights the antimycobacterial potential of biologically synthesized AgNPs,underscoring the possibility of discovering/developing new antimycobacterial agents using biological synthesis approaches with less toxicity and high selectivity.

Immunotherapy of Epstein-Barr Virus Associated Malignancies Using Mycobacterial HSP70 and LMP2A356-364 Epitope Fusion Protein

Epstein-Barr virus infection is strongly associated with a number of malignancies.The EBV latent membrane protein 2A has been implicated as one of the most attractive candidates for immunotherapy of related malignancies.In previous studies,the T cell epitopes of LMP2A have been identified systematically.However,the epitope-based vaccine generally meets inefficient immunogenicity when used in vivo directly,which could be overcome by combination with appropriate adjuvants.Heat shock protein is a natural chaperon,which is able to activate the classical major histocompatibility complex class I antigen-processing pathway(cross-presentation).In this study,a minigene encoding LMP2A356-364(FLYALALLL)was genetically fused to the carboxy-terminal of mycobacterial heat shock protein 70.The epitope fusion protein was expressed and purified,and the cross-presentation of LMP2A_(356-364) by monocyte-derived dendritic cells pulsed with the epitope fusion protein was evaluated.Results showed that the epitope fusion protein-pulsed mDCs were much more efficient than the single peptide-pulsed mDCs on CTL activation.Immunization of HLA-A2.1 transgenic mice with MtHsp70-LMP2A_(356-364) generated peptide specific CTL more effectively than a single peptide plus incomplete Freund's adjuvant(IFA).Growth of LMP2A expressing B16 melanoma tumor cells was suppressed in the vaccinated groups.Our results suggested that MtHsp70-LMP2A_(356-364) fusion protein was more effective than the CD8^(+)T cell epitope alone on anti-tumor immunity.As a result,the MtHsp70-LMP2A_(356-364) fusion protein is considered to be a promising candidate vaccine for EBV related malignancies.

Comparison of Histological, Microbiological, and Molecular Methods in Diagnosis of Patients with TBLN Having Different Anti-TB Treatment Background

Objective The influence of anti-tuberculosis （TB） treatment history on tuberculous lymphadenitis （TBLN） diagnosis is unclear. Therefore, this study aims to evaluate the diagnostic methods, including histology, microbiology, and molecular tests, used for TBLN. Methods In this study, suspected patients with TBLN and having different anti-T8 treatment background were enrolled. All the samples were tested simultaneously by histology, ZiehI-Neelsen （ZN） staining, mycobacterial culture （culture）, Xpert MTB/RIF （xpert）, real-time PCR, and high-resolution melting curve PCR （HRM）. Thereafter, the performance of these methods on samples with different anti-TB treatment background was assessed. Results In our study, 89 patients were prospectively included 82 patients with TBLN and 7 with other diseases. The overall sensitivities of Xpert, real-time PCR, histology, ZN staining, and culture were 86.6%, 69.5%, 58.5%, 43.9%, and 22.0%, respectively. The anti-TB treatment history revealed dramatic influences on the sensitivity of culture （P 〈 0.0001）. In fact, the treatment that lasted over 3 months also influenced the sensitivity of Xpert （P 〈 0.05）. However, the treatment history did not affect the performance of remaining tests （P 〉 0.05）. For rifampicin drug susceptibility test （DST）, the anti-T8 treatment showed only significant influence on the success rate of culture DST （P = 0.001）, but not on those of Xpert and HRM tests （P 〉 0.05）. Conclusion Other tests as welt as culture should be considered for patients with TBLN having retreatment history or over 1-month treatment to avoid false negative results.

Hemophagocytic lymphohistiocytosis caused by STAT1 gain-offunction mutation is not driven by interferon-γ:A case report

BACKGROUND Hemophagocytic lymphohistiocytosis(HLH)is a life-threatening hyperinflammatory syndrome caused by many genetic defects.STAT1 is a DNAbinding factor that regulates gene transcription.HLH caused by STAT1 gain-offunction(GOF)mutations has rarely been reported and its clinical manifestations and mechanisms are not clearly defined.CASE SUMMARY A 2-year-old boy presented to our hospital with recurrent fever for>20 d.The patient had a personal history of persistent oral candidiasis and inoculation site infection during the past 2 years.Hepatosplenomegaly was noted.Complete blood cell count showed severe anemia,thrombocytopenia and neutropenia.Other laboratory tests showed liver dysfunction,hypertriglyceridemia and decreased fibrinogen.Hemophagocytosis was found in the bone marrow.Chest computed tomography showed a cavitary lesion.Tests for fungal infection were positive.Serum T helper(Th)1/Th2 cytokine determination demonstrated moderately elevated levels of interleukin(IL)-6 and IL-10 with normal interferon(IFN)-γconcentration.Mycobacterium bovis was identified in bronchoalveolar lavage fluid by polymerase chain reaction.Genetic testing identified a heterozygous mutation of c.1154C>T causing a T385M amino acid substitution in STAT1.Despite antibacterial and antifungal therapy,the febrile disease was not controlled.The signs of HLH were relieved after HLH-94 protocol administration,except fever.Fever was not resolved until he received anti-tuberculosis therapy.Hematopoietic stem cell transplantation was refused and the patient died six months later due to severe pneumonia.CONCLUSION Patients with STAT1 GOF mutation have broad clinical manifestations and may develop HLH.This form of HLH presents with normal IFN-γlevel without cytokine storm.

Idiopathic tenosynovitis of the wrist with multiple rice bodies: A case report and review of literature

BACKGROUND Multiple rice bodies in the wrist is a rare disorder that requires surgery,and there are still many uncertainties regarding its diagnosis and treatment.CASE SUMMARY We described a rare case of chronic idiopathic tenosynovitis with rice bodies of the wrist in a 71-year-old man and reviewed similar topics in the literature.A total of 43 articles and 61 cases were included in the literature review.Our case had a usual presentation:it was similar to those in the literature.The affected population was mainly older adults,with an average age of 59.43(range,3 to 90)years.The male-to-female ratio was 1.54:1(37/24).Most of them showed limited swelling and pain,only 23.0%had carpal tunnel symptoms,and the average disease duration was 18.03(0.5-60)mo.Wrist flexor tendon sheath involvement was the most common(95.1%,58/61),and only 3 cases had extensor tendon sheath involvement.The main causes were tuberculosis(34.4%,21/61),nontuberculous mycobacteria(24.6%,15/61),idiopathic tenosynovitis(31.1%,19/61),and others(9.84%,6/61).There were 10 patients with recurrences;in 6 of them,were due to non-tuberculous mycobacterial infections.CONCLUSION We reported a case of wrist idiopathic tenosynovitis with rice body formation,and established a clinical management algorithm for wrist tenosynovitis with rice bodies,which can provide some reference for our clinical diagnosis and treatment.The symptoms of rice-body bursitis of the wrist are insidious,nonspecific,and difficult to identify.The aetiology is mainly idiopathic tenosynovitis and mycobacterial(tuberculosis or non-tuberculous)infections;the latter are difficult to treat and require long-duration systemic combination antibiotic therapies.Therefore,before a diagnosis of idiopathic tenosynovitis is made,we must exclude other causes,especially mycobacterial infections.

Mycobacterium avium subspecies paratuberculosis in the etiology of Crohn's disease, cause or epiphenomenon?

The origin of inflammatory bowel disease is unknown. Attempts have been made to isolate a microorganism that could explain the onset of inflammation, but no pathological agent has ever been identified. Johne&#x02019;s disease is a granulomatous chronic enteritis of cattle and sheep caused by Mycobacterium avium subspecies paratuberculosis (MAP) and shows some analogies with Crohn&#x02019;s disease (CD). Several studies have tried to clarify if MAP has a role in the etiology of CD. The present article provides an overview of the evidence in favor and against the &#x0201c;MAP-hypothesis&#x0201d;, analyzing the methods commonly adopted to detect MAP and the role of antimycobacterial therapy in patients with inflammatory bowel disease. Studies were identified through the electronic database, MEDLINE, and were selected based on their relevance to the objective of the review. The presence of MAP was investigated using multiple diagnostic methods for MAP detection and in different tissue samples from patients affected by CD or ulcerative colitis and in healthy controls. On the basis of their studies, several authors support a close relationship between MAP and CD. Although increasing evidence of MAP detection in CD patients is unquestionable, a clear etiological link still needs to be proven.

Antioxidants: Friend or foe for tuberculosis patients

Respiratory burst induced bacteria killing by oxidants are important mechanism of host defence. However, it is impaired in tuberculosis due to inhibition of respiratory burst by Mycobacterial factors. Antioxidants are compounds that cause chelation of reactive oxygen species. So, antioxidants are expected to play a negative role in the management of active tuberculosis. But, oxidative stress is a proved fact that invariably happens in tuberculosis patients which is known to cause immunosuppression. Immunosuppression in turn is expected to augment tuberculosis. Hence, antioxidant supplementation is expected to benefit tuberculosis patients by minimising oxidative stress induced immunosuppression. Therefore, the role of antioxidants in tuberculosis appears to be paradoxical and urgent. Understanding of the role of antioxidant supplementation in tuberculosis is warranted. It is in this context that we have reviewed the recent literature and addressed the problem for its solution.

Ocular tuberculosis associated with Epstein-Barr virus myelitis: A case report

Ocular tuberculosis(OTB)is a chronic eye infection caused by Mycobacterium tuberculosis.Some cases of myelitis are associated with Epstein-Barr virus(EBV),with 1-5%of EBV infections leading to neurologic complications.We describe a 34-year-old Iranian woman with OTB and EBV coinfection.Despite initial success with anti-TB agents,the disease progressed,necessitating enucleation.Mycobacterium tuberculosis was detected by a tuberculin coagulation test,and EBV was confirmed via polymerase chain reaction.MRI showed plaques in the spinal cord and brain.The patient was treated with anti-TB and antiretroviral agents.Recognizing TB in the differential diagnosis of EBV myelitis is crucial.

Value of Metagenomic Next-Generation Sequencing in Clinical Diagnosis and Targeted Therapy of Nontuberculous Mycobacteria Infection

The purpose of this study was to assess the value of metagenomic next-generation sequencing(mNGS)for rapid diagnosis of diseases caused by nontuberculous mycobacteria(NTM).We retrospectively reviewed four NTM-infected cases diagnosed by smear microscopy,mycobacterial culture and mNGS methods.We found that the mNGS method not only had a shorter detection turnaround time(3–4 days)than Mycobacterium culture(15–20 days)but also had higher sensitivity and specificity to identify NTM compared with conventional detection methods.In addition,mNGS was able to identify coinfections by NTM and other bacteria,fungi or viruses.Overall,diagnosis of NTM by mNGS can provide timely and precise guidance for subsequent clinical treatment of NTM infections.

Molecular epidemiology of Mycobacterium tuberculosis in Gansu province of China

Background Mycobacterial interspersed repetitive units-variable number tandem repeat （MIRU-VNTR） and Beijing family typing based on detecting the deletion of RD105 sequence are two common genotyping methods used to study the molecular epidemiologic characteristics of Mycobacterium （M.） tuberculosis. We collected 218 strains of M. tuberculosis between 2004 and 2006 in the Linxia Hui Autonomous Prefecture of Gansu province in Northwest China. Methods MIRU-VNTR analysis and Beijing family typing based on detecting the deletion of RD105 sequence were used to type the 218 strains, and their typing power was evaluated to look for practical and efficient genotyping methods suitable for the region. Results The MIRU typing yielded 115 distinct genotypes, including 98 unique isolates and 17 different clusters containing 120 isolates （55.05%）; the cluster rate was 47.25%. By detecting the deletion of RD105 sequence, 188 of 218 （86.23%） isolates belonged to Beijing family. Combination of Beijing family typing and MIRU typing yielded 118 distinct patterns, including 101 unique isolates and 17 clusters containing 117 isolates （54.13%）. The largest cluster contained 58 strains with MIRU genotype of 223325173533 which contained 50 strains belonging to Beijing family and 8 strains belonging to non-Beijing family. Conclusions The Beijing family strains occupied a large proportion and the Beijing family MIRU genotype 223325173533 is a dominant strain in Linxia of Gansu. Combining detecting the deletion of RD105 and MIRU typing together provides a simple, fast, and effective method which is low in cost and might be practical and suitable for M. tuberculosis aenotvDina in China.