Standard Antituberculosis Therapy Research Articles

The Effect of Immunoglobulin G on the Humoral Immunity in Patients with Tuberculosis/HIV Coinfection.

Previously, an increase in clinical effectiveness of the antituberculosis treatment (ATT) and antiretroviral therapy (ART) in case of additional immunoglobulin G (IgG) administration in patients with multidrug-resistant tuberculosis (MDR-TB)/HIV coinfection was reported. The aim of this study was to investigate the impact of IgG administration in addition to the standard second-line ATT and ART on the humoral immunity status in patients with MDR-TB/HIV coinfection immune deficiency. The study involved 52 patients living with HIV with MDR-TB coinfection and CD4+ lymphocyte cell count below 50 cells/μCL. Patients in the control group and intervention group received the second-line ATT and ART; in addition, patients in the intervention group received IgG intravenously. The humoral immunity status was evaluated by measurement of IgA, IgE, IgG, and IgM in plasma. The standard ATT and ART resulted in a two-step change in humoral immunity: IgM, IgG, IgA, and IgE levels gradually increased to a maximal level at the 5-month mark and started to gradually decrease after the 8-month mark. Addition of IgG to the standard therapy resulted in a steeper decrease in the immunoglobulin level in serum, especially IgG, compared with standard therapy alone, allowing for an earlier initiation of ART in patients in the intervention group.

Diagnosis and treatment of osteo-articular tuberculosis of the foot and ankle (a five case series)

IntroductionOsteo-articular tuberculosis is a rare manifestation of this disease, often posing diagnostic challenges that necessitate additional diagnostic imaging modalities such as radiography, CT, and MRI. This article presents a series of five cases involving tuberculosis affecting the bones of the foot and ankle, diagnosed at various stages. The patients received appropriate anti-tuberculosis medical treatment following national protocols, along with surgical interventions when necessary. Case studiesIn this series, we describe the clinical characteristics and management of five cases of foot and ankle bone tuberculosis. These cases were diagnosed at different stages, and all patients received standard anti-tuberculosis medical therapy according to national treatment guidelines. Surgical interventions were performed when deemed necessary to optimize patient outcomes. DiscussionThe diagnosis of bone tuberculosis should be considered in any clinical scenario that presents with uncertain features, persistent symptoms, or resistance to conventional treatment approaches. It is crucial to employ a multidisciplinary approach involving medical and surgical management to effectively address this challenging disease. However, it is important to note that surgical intervention cannot replace the necessity of proper medical treatment. ConclusionTuberculosis involving the bones of the foot and ankle remains an infrequent occurrence. However, considering the endemic context, prompt therapeutic interventions are essential to prevent significant osteoarticular damage. Early diagnosis, adherence to established treatment protocols, and a comprehensive approach encompassing both medical and surgical modalities are crucial for successful management of this rare entity.

Standard-dose versus double-dose dolutegravir in HIV-associated tuberculosis in South Africa (RADIANT-TB): a phase 2, non-comparative, randomised controlled trial

The drug-drug interaction between rifampicin and dolutegravir can be overcome by supplemental dolutegravir dosing, which is difficult to implement in high-burden settings. We aimed to test whether virological outcomes with standard-dose dolutegravir-based antiretroviral therapy (ART) are acceptable in people with HIV on rifampicin-based antituberculosis therapy. RADIANT-TB was a phase 2b, randomised, double-blind, non-comparative, placebo-controlled trial at a single site in Khayelitsha, Cape Town, South Africa. Participants were older than 18 years of age, with plasma HIV-1 RNA greater than 1000 copies per mL, CD4 count greater than 100 cells per μL, ART-naive or first-line ART interrupted, and on rifampicin-based antituberculosis therapy for less than 3 months. By use of permuted block (block size of 6) randomisation, participants were assigned (1:1) to receive either tenofovir disoproxil fumarate, lamivudine, and dolutegravir plus supplemental 50 mg dolutegravir 12 h later or tenofovir disoproxil fumarate, lamivudine, and dolutegravir plus matched placebo 12 h later. Participants received standard antituberculosis therapy (rifampicin, isoniazid, pyrazinamide, and ethambutol for the first 2 months followed by isoniazid and rifampicin for 4 months). The primary outcome was the proportion of participants with virological suppression (HIV-1 RNA <50 copies per mL) at week 24 analysed in the modified intention-to-treat population. This study is registered with ClinicalTrials.gov, NCT03851588. Between Nov 28, 2019, and July 23, 2021, 108 participants (38 female, median age 35 years [IQR 31-40]) were randomly assigned to supplemental dolutegravir (n=53) or placebo (n=55). Median baseline CD4 count was 188 cells per μL (IQR 145-316) and median HIV-1 RNA was 5·2 log10 copies per mL (4·6-5·7). At week 24, 43 (83%, 95% CI 70-92) of 52 participants in the supplemental dolutegravir arm and 44 (83%, 95% CI 70-92) of 53 participants in the placebo arm had virological suppression. No treatment-emergent dolutegravir resistance mutations were detected up to week 48 in the 19 participants with study-defined virological failure. Grade 3 and 4 adverse events were similarly distributed between the study arms. The most frequent grade 3 and 4 adverse events were weight loss (4/108 [4%]), insomnia (3/108 [3%]), and pneumonia (3/108 [3%]). Our findings suggest that twice-daily dolutegravir might be unnecessary in people with HIV-associated tuberculosis. Wellcome Trust.

Peritoneal and Pulmonary Tuberculosis in a Postpartum Female with Elevated Cancer Antigen 125 and Ascites

Peritoneal tuberculosis is a rare form of extrapulmonary tuberculosis and presents a challenging diagnosis because of its nonspecific clinical manifestations. Peritoneal TB mimics other pathologies, including abdominal carcinomatosis, especially when the patient presents with ascites and an elevated cancer antigen (CA)-125 levels. Case Presentation. A postpartum 20-year-old Hispanic female recently discharged after transverse cesarean surgery, presented to the ER with fever, chills, edema, abdominal distension, nausea, and vomiting. The patient was febrile, tachycardic, and hypotensive. Chest X-ray demonstrated alveolar and interstitial consolidations; chest CT revealed tree-in-bud opacities in the right lower lobe, suggestive of atypical (TB)/fungal infection. CT of the abdomen and pelvis demonstrated ascites, omental thickening, peritoneal thickening, and mesenteric adenopathy, suggestive of carcinomatosis. She was admitted with a presumed diagnosis of sepsis secondary to pneumonia and started empirically on broad-spectrum antibiotics without clinical improvement. A battery of oncology markers was ordered and revealed a mildly elevated cancer antigen (CA)-125. Diagnostic paracentesis showed lymphocytic predominance with positive mycobacteria PCR, elevated adenosine deaminase (ADA), and no malignant cells. Subsequently, the sputum acid-fast bacilli (AFB) stain returned positive for tuberculosis, confirming the diagnosis of pulmonary tuberculosis. A peritoneal biopsy was obtained and demonstrated caseating granulomas consistent with peritoneal tuberculosis. The patient was started on standard antituberculosis therapy with clinical improvement. This case highlights the need for a high-level of suspicion for peritoneal tuberculosis in a patient with pulmonary tuberculosis who presents with intra-abdominal ascites, omental thickening, peritoneal thickening, and mesenteric lymphadenopathy, despite the presence of an elevated CA-125 level.

Preparation and Evaluation of Low-Dose Calcitriol Dry Powder Inhalation as Host-Directed Adjunct Therapy for Tuberculosis.

BackgroundIt is unclear whether Vitamin D is efficacious as a host-directed therapy (HDT) for patients of tuberculosis (TB). We investigated pulmonary delivery of the active metabolite of Vitamin D3, i.e., 1, 25-dihydroxy vitamin D3 (calcitriol) in a mouse model of infection with Mycobacterium tuberculosis (Mtb).MethodsWe optimized a spray drying process to prepare a dry powder inhalation (DPI) of calcitriol using a Quality by Design (QbD) approach. We then compared outcomes when Mtb-infected mice were treated with inhaled calcitriol at 5 ng/kg as a stand-alone intervention versus DPI as adjunct to standard oral anti-tuberculosis therapy (ATT).ResultsThe DPI with or without concomitant ATT markedly improved the morphology of the lungs and mitigated histopathology in both the lungs and the spleens. The number of nodular lesions on the lung surface decreased from 43.7 ± 3.1 to 22.5 ± 3.9 with the DPI alone and to 9.8 ± 2.5 with DPI + ATT. However, no statistically significant induction of host antimicrobial peptide cathelicidin or reduction in bacterial burden was seen with the DPI alone. DPI + ATT did not significantly reduce the bacterial burden in the lungs compared to ATT alone.ConclusionsWe concluded that HDT using the low dose calcitriol DPI contributed markedly to mitigation of pathology, but higher dose may be required to evoke significant induction of bactericidal host response and bactericidal activity in the lung. Supplementary InformationThe online version contains supplementary material available at 10.1007/s11095-022-03360-5.

Lactobacillus casei modulates inflammatory cytokines and metabolites during tuberculosis treatment: A post hoc randomized controlled trial.

Inflammatory cytokines and metabolic abnormalities are common in patients with tuberculosis. Observational studies have indicated that probiotics modulate inflammatory cytokines and metabolites; however, clinical evidence of the effect of probiotics on patients with tuberculosis is lacking. This study investigated the effects of Lactobacillus casei on inflammatory cytokines and metabolites during tuberculosis treatment. A randomized controlled trial was conducted. A total of 47 inpatients were included and randomly assigned to receive standard antituberculosis therapy only (control group) or that treatment together with 1 × 1010 colony-forming units per day of Lactobacillus casei (low-dose group) or 2 × 1010 colony-forming units per day of Lactobacillus casei (high-dose group) for 4 weeks of intensive treatment during hospitalization. Plasma samples were analyzed for inflammatory cytokines and metabolomics with ELISA kits and ultrahigh performance liquid chromatography quadrupole time-of-flight mass spectrometry. Daily Lactobacillus casei supplementation of up to 2 × 1010 colony-forming units significantly lowered the concentrations of tumor necrosis factor-α, interleukin-6, interleukin-10, and interleukin-12 (p=0.007, p=0.042, p=0.002, p<0.001, respectively) in patients with tuberculosis. Compared with the control and low-dose groups, the plasma metabolites of phosphatidylserine, maresin 1, phosphatidylcholine, L-saccharopine, and pyridoxamine were significantly upregulated, and N-acetylmethionine, L-tryptophan, phosphatidylethanolamine, and phenylalanine were downregulated in the high-dose group. Strong correlations were observed between metabolites and inflammatory cytokines. Lactobacillus casei supplementation during the intensive phase of tuberculosis treatment can significantly modulate inflammatory cytokines and metabolites. Decreased inflammatory cytokines may be related to metabolite changes.

АКТИВАЦІЯ ФАГОЦИТАРНОЇ ЛАНКИ ІМУНІТЕТУ ПРИ ЗАСТОСУВАННІ ПРИРОДНОГО ГЕПАТОПРОТЕКТОРУ В КОМПЛЕКСНОМУ ЛІКУВАННІ ХВОРИХ НА ТУБЕРКУЛЬОЗ ЛЕГЕНЬ З ПОБІЧНИМИ РЕАКЦІЯМИ НА МЕДИКАМЕНТИ

Various types of adverse reactions to medications often occur during the treatment of diseases that require the simultaneous administration of several drugs. Methods. To study the effect of the natural hepatoprotector Hepatomunil on immunological and biochemical blood parameters, there was a clinical and laboratory examination of 20 adult patients with pulmonary tuberculosis with a deviation from the norm of at least one blood test of the liver or kidneys function during antituberculosis treatment. Biochemical and immunological research methods were used. The drug Hepatomunil was prescribed in the second month of standard four-component anti-tuberculosis therapy for 20 days. Results. There was a significant decrease in blood levels of cytolytic enzymes AST and ALT after the course of treatment with Hepatomunil which showed an effective hepatoprotective action. The phagocytic number of blood granulocytes increased significantly from (6.3 ± 0.6) units up to (11.2 ± 2.1) units; and the one of blood monocytes did from (6.8 ± 0.7) units up to (11.1 ± 1.7) units also. The drug had no effect on the studied parameters of cellular immunity (CD3+19–, CD4+8–, CD4–8+, CD3–16+, CD3–19+). Conclusions. The drug Hepatomunil demonstrated not only pronounced hepatoprotective, but also immunomodulatory properties when used in the complex therapy of patients with pulmonary tuberculosis. It stimulated the blood phagocytes function by restoring their ingesting capacity (with an increase of the phagocytic number), which is very important in the treatment of patients with chronic lung diseases with infectious agents involved, which are destroyed better when the phagocytic function of blood cells is activated. Key words: immunomodulator, hepatoprotector, hepatotoxic reactions, phagocytosis, pulmonary tuberculosis

Мезенхимные стволовые клетки в терапии туберкулеза

Tuberculosis, caused by the obligate intracellular microorganism Mycobacterium tuberculosis, is one of the oldest known infectious diseases in humans. Modern therapy of tuberculosis, consisting of several antibacterial drugs, is long-term, toxic and requires high compliance from the patient, therefore, the development of new therapeutic strategies that would minimize the duration of treatment and prevent the formation of drug-resistant forms of mycobacteria is relevant and important. Cellular therapy now holds the promise of potential complementary therapeutic options for the treatment of drug-resistant tuberculosis. In recent years, the possibilities of using mesenchymal stem cells in the treatment of tuberculosis of various localization have been widely studied. The use of such cells in conjunction with standard anti-tuberculosis therapy holds great promise for shortening the duration of treatment and reducing the formation of drug-resistant mycobacteria. This article describes the possibilities of using mesenchymal stem cells in the treatment of tuberculosis in patients, including those with extensive and multidrug resistance, as well as the mechanisms of interaction of mesenchymal stem cells with M. tuberculosis.

The association between osteopontin and tuberculosis: A systematic review and meta-analysis.

We examined the data reported in the studies for comparison of osteopontin (OPN) levels in tuberculosis and healthy participants, and to discuss whether OPN could be extended to disease diagnosis, severity assessment and therapeutic effect monitering. A systematic literature search was conducted in PubMed, EMBASE, Scopus, the Cochrane Library, Web of Science, the China National Knowledge Infrastructure (CNKI) and WanFang databases. The pooled risk estimates were shown in standardized mean difference (SMD) with 95% confidence interval (CI) for OPN levels. The random effect model was used according to the test of heterogeneity among studies. Subgroup analyses and meta-regression models were performed to identify the possible sources of heterogeneity. 17 retrospective studies with 933 tuberculosis participants and 786 healthy controls were finally included in this article. In the primary meta-analysis, higher serum/plasma OPN levels were found in tuberculosis patients (SMD = 2.58, 95%CI = 2.09~3.08, P<0.001). Besides, pooled results from positive acid-fast bacilli (AFB) staining and imaging-severe tuberculosis group demonstrated higher OPN concentrations (SMD = 0.90, 95%CI = 0.58~1.21, P<0.001; SMD = 1.11, 95%CI = 0.90~1.33, P<0.001; respectively), and OPN levels decreased after two months of standard anti-tuberculosis therapy (SMD = 2.10, 95%CI = 1.36~2.85, P<0.001). Elevated serum/plasma OPN levels may be associated with an increased risk of tuberculosis, while further well-designed studies are needed. Moreover, OPN could be considered as a potential biomarker for tuberculosis surveillance and severity assessment.

Clinical study of movable external fixation for elbow tuberculosis

To compare clinical effect of movable external fixation and fusion fixation for the treatment of elbow tuberculosis. From October 2013 to June 2019, 52 patients with elbow tuberculosis treated with standard antituberculosis therapy were divided into movable external fixation group and fusion fixation group according to treatment methods. In group A, there were 25 patients, including 11 males and 14 females, aged from 24 to 75 years old with an average of (42.81± 9.01) years old; the courses of diseases ranged from 2 to 9 months with an average of (3.96±1.45) months. In group B, there were 27 patients, including 15 males and 12 females, aged from 23 to 77 years old with an averageof (44.08±7.44) years old; the courses of diseases ranged from 2 to 7 months with an average of (3.88±1.67) months. All patients were performed focus debridement. Intraoperative blood loss, operative time were compared between two groups. VAS score before operation, 2 weeks and 12 months after operation were applied to evaluate pain relieve;Mayo elbow performance score (MEPS) before operation, 1 and 12 months after operation were used to evaluate clinical effect;changes of erythrocyte sedimentation rate (ESR) and Creactive protein, CRP) before operation, 3 weeks after antituberculosis therapy, 1 week and 6 months after operation were compared between two groups. All patients were followed up from 12 to 20 months with an average of (13.50±4.85) months. No mixed infection and recurrence of tuberculosis occurred. There were no statistical differences in intraoperative blood loss and operative time(P>0.05). There was difference in postoperative VAS score at 2 weeks between movable external fixation group (5.15±0.95) and fusion fixation group (4.04±0.84)(P<0.01);while no difference in postoperative VAS score at 12 months between two groups (P>0.05). No difference in ESR and CRP level between two groups before and after operation (P>0.05). Postoperative Mayo score at 1 and 12 months in movable external fixation group were (78.15±7.83) and (90.19±7.13);in fusion fixation group were (70.40±7.61) and (82.60±8.38);there were differences in Mayo score at different time points between two groups(P<0.01). For elbow tuberculosis, movable external fixation and fusion fixation have equal effect in operative time, amount of bleeding and control of tuberculosis infection indicator. Movable external fixation need earlier functional exercise, not conducive to pain relief at early stage, which may be better than fusion fixation, it is worth clinical promoting.

Medication management of autonomic nervous system disorders in adolescents with tuberculosis

To manage autonomic disorders in adolescents with tuberculosis, 100 people from 12 to 15 years old were examined and randomly divided into two groups: Group 1 received standard anti-tuberculosis therapy, and in Group 2, additionally to standard therapy, comprehensive treatment with Magne B6was used for 2 months, and then Valerian extract was used for another 2 months. For comparison, 50 healthy adolescents were examined. Before treatment, all adolescents with tuberculosis experienced a decrease in heart rate variability, a pronounced autonomic imbalance with the prevalence of sympathicotonia and overexertion of compensatory mechanisms. In Group 1, during the comprehensive treatment there were an increase in SDNN and Mo and decrease in AMo and tension index at rest. Active orthostatic test (AOT) was accompanied by a significant increase in SDNN, Mo and a decrease in AMo, which indicated an increase in the activity of the parasympathetic autonomic nervous system and decreased activity of the sympathetic autonomic nervous system. In the group receiving standard therapy, hypersympathycotonia persisted and manifested through significant (p &lt; 0.05) reduction in such parameters as SDNN, increased heart rate, AMo, and Mo shift to short intervals. Medication management resulted in the vegetative balance by increasing heart rate variability, reducing hypersympathicotonia, improving the autonomic support of the cardiovascular system at rest and during AOT.

Tuberculose pulmonaire sous traitement par immunothérapie type anti-PD1

Immunotherapy is now a standard of care in oncology. There is a need to improve our knowledge about immune-related adverse events, especially infectious diseases. We describe the case of a 49-year old male who received anti-PD1 therapy, to treat metastatic melanoma with pulmonary metastasis. After 3 cycles of nivolumab, computed tomography scanning showed a decrease of the pulmonary metastasis in the upper left lobe, but revealed new pulmonary lesions such as tree-in-bud and a lung cavity in the same lobe. This was diagnosed as pulmonary tuberculosis with no antibiotic resistance identified. The patient continued the immunotherapy and was initiated onto a standard anti-tuberculosis therapy. In the absence of an initial positive IFN-γ release assay (Quantiferon) test, but as there might have been a history of primary infection during childhood, a reactivation of tuberculosis was considered to be likely. This is the ninth case of tuberculosis infection under immunotherapy and it underlines the need to consider infection risks in patients undergoing immunotherapy. An INF-γ release assay screening test should be considered an essential part of the pre-treatment work-up.

Longitudinal cerebrospinal fluid assessment in a patient with tuberculous meningitis—A case report

BackgroundDynamic assessment of cerebrospinal fluid (CSF) is essential for diagnosis, treatment, and prognosis of tuberculous meningitis, one of the most severe forms of central nervous system (CNS) infection.Case presentationA 45‐year‐old man sought care as he developed confusion, clonic convulsion, and coma. Longitudinal, comprehensive analyses of cytological, biochemical, and microbial changes in CSF specimen were assessed for this patient. On day 1 of hospitalization, modified Ziehl‐Neelsen staining of CSF identified positive acid‐fast bacilli, cytological analysis revealed neutrophilic‐predominant pleocytosis (neutrophils 77%), and adenosine deaminase (ADA) was substantially elevated. Therefore, tuberculous meningitis was diagnosed and first‐line standard anti‐tuberculosis treatment was initiated. Interestingly, after 7‐day treatment, the patient was greatly improved, and CSF disclosed a dominant percentage of lymphocytes (82%) as well as macrophages engulfing Mycobacterium tuberculosis. Later, the dose of dexamethasone was reduced, large number of neutrophils (57%) was present and protein level was immediately elevated in CSF specimen, indicating a possible relapse of tuberculous meningitis. Since the clinical condition of the patient was not worsening, the patient was stick to reduced dose of dexamethasone and standard anti‐tuberculosis agents. He was discharged from the hospital on day 34, with 1‐year continuation standard anti‐tuberculosis therapy, and was clinically resolved from tuberculous meningitis.ConclusionDetailed analyses of cellular composition, biochemical results, and microbial tests of CSF specimen provide the physician direct evidence of the immune surveillance status during tuberculous meningitis, which facilitates early diagnosis, optimal treatment, and improved prognosis.

Vitamin D as an Adjunctive Treatment to Standard Drugs in Pulmonary Tuberculosis Patients: An Evidence-Based Case Report.

Background Vitamin D has a prominent role in the body's innate immunity as it is important in the maintenance of macrophages and monocytes and its function in defending against infections. In-vitro studies have established vitamin D's potential role in tuberculosis (TB) infection, in that it restricts Mycobacterium tuberculosis growth, thus implying the potential benefit of vitamin D as an adjunctive treatment for TB. However, clinical trials and reviews have contradicting findings regarding the true clinical efficacy of adjunctive vitamin D, particularly in reducing the sputum conversion rate (SCR). Objective This study aims to update the current evidence regarding vitamin D supplementation as an adjunctive treatment in achieving the smear sputum conversion rate (SCR) among pulmonary TB patients. Method A comprehensive search was conducted in October 2018 in PubMed-NCBI, MEDLINE-OVID, SCOPUS-Elsevier, and Cochrane. The selection of studies was done as per the predetermined inclusion and exclusion criteria of this EBCR and resulted in the inclusion of 11 eligible studies (8 RCTs and 3 systematic reviews). The selected studies were then critically appraised for their validity, importance, and applicability according to the CEBM (Centre for Evidence-Based Medicine) appraisal tools. Results Overall, most of the trials showed no statistically significant changes in terms of the proportion of TB patients with a negative sputum smear conversion in the group treated with an adjunctive therapy vs. the group treated with standard antituberculosis therapy alone. Only one trial showed significant results, which was conducted in a population of TB patients with vitamin D deficiency. Furthermore, overall the reviews showed no significant change in the 8-week sputum smear conversion after treatment within the group given vitamin D in comparison to those who were not. Conclusion Vitamin D as adjunctive therapy in TB patients shows no clinical improvement in terms of sputum conversion to antituberculosis management.

Clinical Characteristics and Treatment Outcomes of Definitive Versus Standard Anti-Tuberculosis Therapy in Patients with Tuberculous Lymphadenitis.

Although it is necessary to culture Mycobacterium tuberculosis from tuberculous lymphadenitis (TBL) patients for definitive therapy, based on the drug-sensitivity test (DST), substantial cases remain culture-negative. Limited data are available regarding the treatment outcomes after standard anti-tuberculosis therapy in culture-negative TBL. The aim of this study was to compare the recurrence rates between definitive anti-tuberculosis therapy, based on DST and standard anti-tuberculosis therapy in culture-negative TBL. A multicenter retrospective cohort study was performed from 2011 to 2015 in South Korea. The study population was divided into two groups according to treatment type. A total of 234 patients with TBL were analyzed, who were treated with definitive (84 patients) and standard anti-tuberculosis (150 patients) therapy, respectively. During a 28.0 (24.0–43.0) month follow-up period, nine cases (3.8%) had recurrence of TB after treatment completion. The recurrence rate was not significantly different between the two groups (2/84, 2.4% in definitive anti-tuberculosis therapy group versus 7/150, 4.7% in standard anti-tuberculosis therapy group, p = 0.526). The recurrence in all nine cases was diagnosed as clinical recurrence rather than microbiological recurrence. Therefore, culture-negative TBL can be treated with standard anti-TB medication, although DST is not available but clinically stable after initiation of treatment.

Diagnosis and treatment of pancreatic tuberculosis: experiences of 10 cases

Objectives: To study the clinical characteristics of pancreatic tuberculosis, and therefore to improve the diagnosis and treatment of this disease. Methods: The clinical data of 10 patients with pancreatic tuberculosis form 1990 to 2017 were reviewed, including clinical characteristics, laboratory tests and imaging features. Results: The ten patients aged 28 to 71 (median 56) years. All of them presented varying degrees of abdominal pain and weight loss (3 to 8 kg). Hypo-echoic pancreatic masses were shown by abdominal ultra-sound in 7 cases, and cystic-solid masses with thick wall was shown by abdominal CT scan in 4 cases, but dilatation of the pancreatic duct was found in none of the 10 cases. Hemoglobin levels lower than 12 g/L were found in 6 cases, and ESR more than 20 mm/1 h was present in 7 cases. Four cases received PPD test, but only one was positive. CA19-9 was found to be higher than normal (27 IU/ml) in 3 cases (39.2 IU/ml, 125.7 IU/ml, 88.9 IU/ml respectively). Three cases received T-spot.TB tests, and all the results were positive. Seven cases received laparotomy, and the other 3 received endoscopic ultrasound-guided biopsy. Caseous necrosis and Langerhans cells were found in all the 10 cases. Nine patients were treated by 6 to 12 months' anti-tuberculosis therapies, and at 1-5 years' follow-up, 8 were cured and 1 improved. Conclusions: The manifestations of pancreatic tuberculosis were easy to be confused with other diseases, and therefore a comprehensive understanding of history and careful examinations were important for a correct diagnosis. Once the diagnosis was made, prompt standard anti-tuberculosis therapy could lead to a favorable outcome.

Elevated levels of matrix metalloproteinases reflect severity and extent of disease in tuberculosis-diabetes co-morbidity and are predominantly reversed following standard anti-tuberculosis or metformin treatment

BackgroundMatrix metalloproteinases (MMPs) are considered to be key mediators of tuberculosis (TB) pathology but their role in tuberculosis – diabetes comorbidity (TB-DM) is not well understood.MethodsTo study the association of MMP levels with severity and extent of disease as well as bacterial burden in TB-DM, we examined the systemic levels of MMP-1, − 2, − 3, − 7, − 8, − 9, − 10, − 12 and − 13 in individuals with TB-DM and compared them to those with TB alone (TB) or healthy controls (HC).ResultsCirculating levels of MMP-1, − 2, − 3, − 7, − 10 and − 12 were significantly higher in TB-DM compared to both TB and HC and MMP -13 levels were higher in comparison to HC alone. To understand the effect of standard anti-tuberculosis therapy (ATT) on these MMP levels in TB-DM, we measured the levels of MMPs at the end of treatment (post-treatment). Our findings indicate that ATT is associated with a significant reduction in the levels of MMP-1, − 2, − 3, − 8 and − 13 post-treatment. Moreover, the levels of MMP-1, − 2, − 3, − 9 and − 12 were significantly higher in TB-DM individuals with cavitary disease and/or bilateral disease at baseline but not post-treatment. Similarly, the levels of MMP -1, − 2, − 3 and − 8 exhibited a significant positive relationship with bacterial burden and HbA1c levels at baseline but not post-treatment. Within the TB-DM group, those known to be diabetic before incident TB (KDM) exhibited significantly higher levels of MMP-1, − 2, − 10 and − 12 at baseline and of MMP-1 and -3 post-treatment compared to those newly diagnosed with DM (NDM). Finally, KDM individuals on metformin treatment exhibited significantly lower levels of MMP-1, − 2, − 3, − 7, − 9 and − 12 at baseline and of MMP-7 post-treatment.ConclusionsOur data demonstrate that systemic MMP levels reflect baseline disease severity and extent in TB-DM, differentiate KDM from NDM and are modulated by ATT and metformin therapy.

Efficacy and safety of cholecalciferol-augmented anti-tuberculosis therapy for treatment of naïve patients with pulmonary tuberculosis: A randomized, controlled, clinical study

Background/objectiveVitamin D deficiency may contribute to the therapeutic failure of antituberculosis therapy (ATT). The aim of this study is to explore the role of adding cholecalciferol to the standard ATT in improving the therapeutic outcome among the naïve patients with pulmonary tuberculosis (TB). MethodsA randomized, controlled, clinical study, which included 496 naïve patients with pulmonary TB, was carried out. The patients were randomly allocated to two groups. Group-A included 247 patients who received ATT, while group-B included 249 patients who received ATT with cholecalciferol. ResultsThe rate of therapeutic failure among the study population was 29.4%; it was significantly lower among patients of group-B compared to those of group-A (22.1% (95% CI 14.7–26.2) vs 38.1% (95% CI 31.5–46.1), p 0.036). In addition, the rate of early therapeutic response was significantly higher among patients of group-B compared to those of group-A (35.3% (95% CI 29.6–42.3) vs 19.4% (95% CI 15.1–24.6), p 0.041). Incidence rate of adverse effects was 19.3%; it was higher (although not statistically significant) among patients of group-A compared to those of group-B (21.9% vs 16.9%). ConclusionsIn conclusion, cholecalciferol-augmented ATT can be more efficacious in treating naïve patients with pulmonary TB compared to the standard ATT. In addition, adding vitamin D3 to ATT provides extra protection against the hepatic and muscular adverse effects of ATT.

Evidence‐based consensus on opportunistic infections in inflammatory bowel disease

Evidence‐based consensus on opportunistic infections in inflammatory bowel disease

Primary tuberculosis of cystic duct lymph node

Tuberculosis (TC) is very common and significant cause of morbidity and mortality worldwide. Isolated cystic duct lymph node TC cases without involvement of gallbladder are exceedingly rare. It is difficult...