Care-seeking pathways and diagnostic delays in extrapulmonary TB patients.

SETTING: This study was conducted at a private tertiary hospital engaged with the TB control programme in the city of Lahore, Pakistan. OBJECTIVE: To assess the healthcare-seeking pathways, different delays and factors associated with delays among the patients who presented in the outpatient department with tuberculous lymphadenitis and pleuritis, the most common manifestations of extrapulmonary TB. DESIGN: This cross-sectional study was conducted prospectively from April 2016 to August 2017. RESULTS: The median age of the 339 patients analysed was 22 years (IQR 17-30); tuberculous lymphadenitis was predominant in females (63%), while pleuritis affected more males (64%). Overall, 62% reported seeking care from healthcare providers before diagnosis, of whom 62% sought care from private facilities, 32% visited facilities >2 times and 8% visited traditional healers. Diagnostic delay was associated with tuberculous lymphadenitis, age 15-44 years, poor socio-economic status and poor TB knowledge. CONCLUSION: There was considerable delay in the management of extrapulmonary TB patients, and the health-system delay was the major contributor, leading to increased patient suffering. Efforts towards minimising health-system delay need to be prioritised for patient screening and diagnosis, with a feasible algorithm that is workable in resource-limited settings.

CONTEXTE: Cette étude a été menée dans un hôpital tertiaire privé participant au programme de lutte contre la TB dans la ville de Lahore, au Pakistan. OBJECTIF: Évaluer les parcours de recherche de soins, les différents délais et les facteurs associés aux délais parmi les patients qui se sont présentés au service des consultations externes avec une lymphadénite et une pleurite tuberculeuses, les manifestations les plus courantes de la TB extrapulmonaire. MÉTHODE: Cette étude transversale a été menée prospectivement d'avril 2016 à août 2017. RÉSULTATS: L'âge médian des 339 patients analysés était de 22 ans (IQR 17­30) ; la lymphadénite tuberculeuse prédominait chez les femmes (63%), tandis que la pleurite touchait davantage les hommes (64%). Dans l'ensemble, 62% des patients ont déclaré avoir eu recours à des prestataires de soins de santé avant le diagnostic, dont 62% dans des établissements privés, 32% ont visité des établissements >2 fois et 8% ont consulté des guérisseurs traditionnels. Le retard de diagnostic était associé à la lymphadénite tuberculeuse, à l'âge de 15 à 44 ans, à un statut socio-économique défavorable et à un manque de connaissances sur la TB. CONCLUSION: La prise en charge des patients atteints de TB extrapulmonaire accuse un retard considérable, dont le système de santé est le principal responsable, ce qui accroît les souffrances des patients. Les efforts visant à minimiser le retard du système de santé doivent être priorisés pour le dépistage et le diagnostic des patients, avec un algorithme réalisable dans des environnements aux ressources limitées.

Prolonged Gastrointestinal Manifestations After Recovery From COVID-19.

BACKGROUND & AIMS: Acute enteric infections are well known to result in long-term gastrointestinal (GI) disorders. Although COVID-19 is principally a respiratory illness, it demonstrates significant GI tropism, possibly predisposing to prolonged gut manifestations. We aimed to examine the long-term GI impact of hospitalization with COVID-19. METHODS: Nested within a large-scale observational cohort study of patients hospitalized with COVID-19 across North America, we performed a follow-up survey of 530 survivors 12-18 months later to assess for persistent GI symptoms and their severity, and for the development of disorders of gut-brain interaction (DGBIs). Eligible patients were identified at the study site level and surveyed electronically. The survey instrument included the Rome IV Diagnostic Questionnaire for DGBI, a rating scale of 24 COVID-related symptoms, the Gastrointestinal Symptoms Rating Scale, and the Impact of Events-Revised trauma symptom questionnaire (a measure of posttraumatic stress associated with the illness experience). A regression analysis was performed to explore the factors associated with GI symptom severity at follow-up. RESULTS: Of the 530 invited patients, 116 responded (52.6% females; mean age, 55.2 years), and 73 of those (60.3%) met criteria for 1 or more Rome IV DGBI at follow-up, higher than the prevalence in the US general population (P < .0001). Among patients who experienced COVID-related GI symptoms during the index hospitalization (abdominal pain, nausea, vomiting, or diarrhea), 42.1% retained at least 1 of these symptoms at follow-up; in comparison, 89.8% of respondents retained any (GI or non-GI) COVID-related symptom. The number of moderate or severe GI symptoms experienced during the initial COVID-19 illness by self-report correlated with the development of DGBI and severity of GI symptoms at follow-up. Posttraumatic stress disorder (Impact of Events-Revised score ≥33) related to the COVID-19 illness experience was identified in 41.4% of respondents and those individuals had higher DGBI prevalence and GI symptom severity. Regression analysis revealed that higher psychological trauma score (Impact of Events-Revised) was the strongest predictor of GI symptom severity at follow-up. CONCLUSIONS: In this follow-up survey of patients 12-18 months after hospitalization with COVID-19, there was a high prevalence of DGBIs and persistent GI symptoms. Prolonged GI manifestations were associated with the severity of GI symptoms during hospitalization and with the degree of psychological trauma related to the illness experience.

Radiofrequency ablation for the management of pancreatic mass lesions.

PURPOSE OF REVIEW: Patients with pancreatic tumors may have limited treatment options. Pancreatic tumor ablation is a novel and emerging treatment modality which can now be performed using endoscopic ultrasound (EUS) guidance. This modality is well suited to guide energy delivery for radiofrequency ablation (RFA) and microwave ablation. These approaches provide minimally invasive, nonsurgical methods for delivering energy to ablate pancreatic tumors in situ . This review summarizes the current data and safety profile for ablation in managing pancreatic cancer and pancreatic neuroendocrine tumors. RECENT FINDINGS: RFA uses thermal energy to induce cell death by coagulative necrosis and protein denaturation. Studies have reported increased overall survival in patients with pancreatic tumors treated with EUS-guided RFA in a multimodality systemic approach and when used in palliative surgeries. Radiofrequency ablation may have corollary benefits in inducing an immune-modulatory effect. Tumor marker carbohydrate antigen 19-9 has been reported to decrease in response to RFA. Microwave ablation is an emerging modality. SUMMARY: RFA utilizes focal thermal energy to induce cell death. RFA has been applied through open, laparoscopic, and radiographic modalities. EUS-guided approaches are now allowing RFA and microwave ablation to be performed for pancreatic tumors in situ .

Combined Drainage and Protocolized Necrosectomy Through a Coaxial Lumen-apposing Metal Stent for Pancreatic Walled-off Necrosis: A Prospective Multicenter Trial.

OBJECTIVE: We evaluated a protocolized endoscopic necrosectomy approach with a lumen-apposing metal stent (LAMS) in patients with large symptomatic walled-off pancreatic necrosis (WON) comprising significant necrotic content, with or without infection. SUMMARY BACKGROUND DATA: Randomized trials have shown similar efficacy of endoscopic treatment compared with surgery for infected WON. DESIGN: We conducted a regulatory, prospective, multicenter single-arm clinical trial examining the efficacy and safety of endoscopic ultrasound -guided LAMS with protocolized necrosectomy to treat symptomatic WON ≥6 cm in diameter with >30% solid necrosis. After LAMS placement, protocolized WON assessment was conducted and endoscopic necrosectomy was performed for insufficient WON size reduction and persistent symptoms. Patients with radiographic WON resolution to ≤ 3 cm and/or 60-day LAMS indwell had LAMS removal, then 6-month follow-up. Primary endpoints were probability of radiographic resolution by 60 days and procedure-related serious adverse events. RESULTS: Forty consecutive patients were enrolled September 2018 to March 2020, of whom 27 (67.5%) were inpatients and 19 (47.5%) had clinical evidence of infection at their index procedure. Mean WON size was 15.0 ± 5.6 cm with mean 53.2% ± 16.7% solid necrosis. Radiographic WON resolution was seen in 97.5% (95% CI, 86.8%, 99.9%) by 60 days, without recurrence in 34 patients with 6-month follow-up data. Mean time to radiographic WON resolution was 34.1 ± 16.8 days. Serious adverse events occurred in 3 patients (7.5%), including sepsis, vancomycin-resistant enterococcal bacteremia and shock, and upper gastrointestinal bleeding. There were no procedure-related deaths. CONCLUSIONS: Endoscopic ultrasound-guided drainage with protocolized endoscopic necrosectomy to treat large symptomatic or infected walled-off necrotic pancreatic collections was highly effective and safe. Clinicaltrials.-gov no: NCT03525808.

Wiskott Aldrich Syndrome: A Multi-Institutional Experience From India.

Background: Wiskott Aldrich syndrome (WAS) is characterized by bleeding manifestations, recurrent infections, eczema, autoimmunity, and malignancy. Over the last decade, improved awareness and better in-house diagnostic facilities at several centers in India has resulted in increased recognition of WAS. This study reports collated data across major primary immunodeficiency diseases (PID) centers in India that are involved in care of children with WAS and highlights the varied clinical presentations, genetic profile, and outcomes of patients in India. Methods: Request to share data was sent to multiple centers in India that are involved in care and management of patients with PID. Six centers provided requisite data that were compiled and analyzed. Results: In this multi-institutional cohort, clinical details of 108 patients who had a provisional diagnosis of WAS were received. Of these, 95 patients with 'definite WAS' were included Fourteen patients were classified as XLT and 81 patients as WAS. Median age at onset of symptoms of patients was 3 months (IQR 1.6, 6.0 months) and median age at diagnosis was 12 months (IQR 6,48 months). Clinical profile included bleeding episodes (92.6%), infections (84.2%), eczema (78.9%), various autoimmune manifestations (40%), and malignancy (2.1%). DNA analysis revealed 47 variants in 67 cases. Nonsense and missense variants were the most common (28.4% each), followed by small deletions (19.4%), and splice site defects (16.4%). We also report 24 novel variants, most of these being frameshift and nonsense mutations resulting in premature termination of protein synthesis. Prophylactic intravenous immunoglobulin (IVIg) was initiated in 52 patients (54.7%). Hematopoietic stem cell transplantation (HSCT) was carried out in 25 patients (26.3%). Of those transplanted, disease-free survival was seen in 15 patients (60%). Transplant related mortality was 36%. Outcome details were available for 89 patients. Of these, 37% had died till the time of this analysis. Median duration of follow-up was 36 months (range 2 weeks- 12 years; IQR 16.2 months- 70 months). Conclusions: We report the first nationwide cohort of patients with WAS from India. Bleeding episodes and infections are common manifestations. Mortality continues to be high as curative therapy is not accessible to most of our patients.

Digestive Manifestations in Patients Hospitalized With Coronavirus Disease 2019.

BACKGROUND & AIMS: The prevalence and significance of digestive manifestations in coronavirus disease 2019 (COVID-19) remain uncertain. We aimed to assess the prevalence, spectrum, severity, and significance of digestive manifestations in patients hospitalized with COVID-19. METHODS: Consecutive patients hospitalized with COVID-19 were identified across a geographically diverse alliance of medical centers in North America. Data pertaining to baseline characteristics, symptomatology, laboratory assessment, imaging, and endoscopic findings from the time of symptom onset until discharge or death were abstracted manually from electronic health records to characterize the prevalence, spectrum, and severity of digestive manifestations. Regression analyses were performed to evaluate the association between digestive manifestations and severe outcomes related to COVID-19. RESULTS: A total of 1992 patients across 36 centers met eligibility criteria and were included. Overall, 53% of patients experienced at least 1 gastrointestinal symptom at any time during their illness, most commonly diarrhea (34%), nausea (27%), vomiting (16%), and abdominal pain (11%). In 74% of cases, gastrointestinal symptoms were judged to be mild. In total, 35% of patients developed an abnormal alanine aminotransferase or total bilirubin level; these were increased to less than 5 times the upper limit of normal in 77% of cases. After adjusting for potential confounders, the presence of gastrointestinal symptoms at any time (odds ratio, 0.93; 95% CI, 0.76-1.15) or liver test abnormalities on admission (odds ratio, 1.31; 95% CI, 0.80-2.12) were not associated independently with mechanical ventilation or death. CONCLUSIONS: Among patients hospitalized with COVID-19, gastrointestinal symptoms and liver test abnormalities were common, but the majority were mild and their presence was not associated with a more severe clinical course.

Primary drug resistance in extra-pulmonary tuberculosis: a hospital-based prospective study from Pakistan.

SETTING: Tertiary level specialised tuberculosis (TB) hospital.OBJECTIVE: To determine the prevalence of antimicrobial resistance in new extra-pulmonary tuberculosis (EPTB) cases.DESIGN: Prospective cross-sectional study. Presumptive EPTB patients with enlarged lymph nodes or pleural effusion having no history of TB treatment were enrolled. Specimens were tested for smear, Xpert® MTB/RIF and culture. Indirect drug susceptibility testing (DST) was performed using MGIT 960 and line-probe assays (LPA).RESULTS: Among 671 cases, 255 were bacteriologically confirmed and 185 DSTs were performed. Multidrug resistance (MDR-TB) was reported in 2.2% (95%CI 0.6-5.4), any resistance to rifampicin (RMP) in 2.7% (95%CI 0.9-6.2), isoniazid (INH) in 7.6% (95%CI 4.1-12.4), ethambutol in 1.1% (95%CI 0.1-3.9), pyrazinamide in 2.2% (95%CI 0.9-5.5) and fluoroquinolones (FQ) in 6.0% (95%CI 3.0-10.4). The sensitivity and specificity of LPA-DST was 100% and >98.8% respectively for RMP, INH and FQ. Among 82 cases with RMP of the results available for all three methods used, five were reported to be resistant on Xpert but all five were susceptible on MGIT 960 and four on MTBDRplus.CONCLUSION: Prevalence of RMP resistance in new EPTB cases is 2.7% (95%CI 0.9-6.2). Caution is warranted for RMP resistance detected using Xpert in EPTB samples with a very low bacterial load.

Functional rescue in a mouse model of congenital muscular dystrophy with megaconial myopathy.

Congenital muscular dystrophy with megaconial myopathy (MDCMC) is an autosomal recessive disorder characterized by progressive muscle weakness and wasting. The observation of megamitochondria in skeletal muscle biopsies is exclusive to this type of MD. The disease is caused by loss of function mutations in the choline kinase beta (CHKB) gene which results in dysfunction of the Kennedy pathway for the synthesis of phosphatidylcholine. We have previously reported a rostrocaudal MD (rmd) mouse with a deletion in the Chkb gene resulting in an MDCMC-like phenotype, and we used this mouse to test gene therapy strategies for the rescue and alleviation of the dystrophic phenotype. Introduction of a muscle-specific Chkb transgene completely rescues motor and behavioral function in the rmd mouse model, confirming the cell-autonomous nature of the disease. Intramuscular gene therapy post-disease onset using an adeno-associated viral 6 (AAV6) vector carrying a functional copy of Chkb is also capable of rescuing the dystrophy phenotype. In addition, we examined the ability of choline kinase alpha (Chka), a gene paralog of Chkb, to improve dystrophic phenotypes when upregulated in skeletal muscles of rmd mutant mice using a similar AAV6 vector. The sum of our results in a preclinical model of disease suggest that replacement of the Chkb gene or upregulation of endogenous Chka could serve as potential lines of therapy for MDCMC patients.

Haploidentical Stem Cell Transplantation: A Gateway to Infrequent Availability of HLA-Matched Related Donors.

Haploidentical stem cell transplantation provides a plausible alternative for the patients when a fully matched donor is unavailable. Historically, the decision of considering haploidentical transplant has remained elusive; however, with the recent advances, the consideration of haploidentical grafts as a treatment option has become more apparent for both allografting for diseases and engraftment failure. We are reporting here an anecdotal case of a successful haploidentical engraftment in a patient with the prior graft failure of an HLA-matched related donor. Since the patient was severely alloimmunized, desensitization protocol was utilized before the haploidentical transplant, and the patient after 8 months of her second allogeneic transplantation is doing great with successful engraftment, no relapse, and no graft-versus-host disease (GVHD). Numerous reports pertinent to haploidentical graft have shown favorable outcomes in the graft placement, a decline in the rate of GVHD, and an improvement in the morbidity and mortality in affected individuals. Based on the current reports, haploidentical transplantation might be more feasible and has meaningful implications in the situations where matched donors are infrequent.

Sleep Fainting: A Neurocardiogenic Entity.

Fainting is a common clinical presentation, with vagally mediated (neurocardiogenic) causes being the most common for syncope presentation to the emergency room, and for hospital admissions. Classic teaching is that upright posture is a prerequisite for vagally mediated syncope (VMS) and that syncope in the supine position has more sinister causes. We present five patients, three males and two females, with a mean age of 44.4 (range 29-67) years, who presented with VMS in the supine position (sleep fainting). Four patients also had a history of classic upright syncope. Based on their clinical features and thorough investigations, we excluded other causes of loss of consciousness and diagnosed these patients to be having VMS in the supine position (sleep fainting). We further describe the management and follow-up of these patients. Sleep fainting/syncope is a new entity and has to be recognized for appropriate management. A diagnosis can be established if there is clinical suspicion, preserved left ventricular function without evidence of coronary artery disease, no high-risk electrocardiographic evidence of pre-excitation, long or short QT syndrome, Brugada syndrome or arrhythmogenic right ventricular dysplasia, and normal neurological work-up.

Extraction and quantification of polyphenols from kinnow (Citrus reticulate L.) peel using ultrasound and maceration techniques.

An investigation was carried out to extract polyphenols from the peel of kinnow (Citrus reticulate L.) by maceration and ultrasound-assisted extraction (UAE) techniques. The antioxidant potential of these polyphenols was evaluated using ferric reducing antioxidant power (FRAP), 2,2-diphenyl-1-picrylhydrazyl (DPPH), and superoxide radical scavenging assays; and their antimicrobial activity was assessed against bacterial strains Staphyloccoccus aureus, Bacillus cereus, and Salmonella typhimurium. The highest extraction yield was obtained through the solvent ethanol at 80% concentration level, whereas UAE was a more efficient technique and yielded comparatively higher polyphenol contents than maceration. Maximum polyphenols were extracted with 80% methanol [32.48 mg gallic acid equivalent (GAE)/g extract] using UAE, whereas minimum phenolics (8.64 mg GAE/g extract) were obtained with 80% ethyl acetate through the maceration technique. Elevated antioxidant activity of kinnow peel extracts was exhibited in three antioxidant assays, where 80% methanolic extracts showed the highest antioxidant activity (27.67±1.11mM/100 g for FRAP) and the highest scavenging activity, 72.83±0.65% and 64.80±0.91% for DPPH and superoxide anion radical assays, respectively. Strong correlations between total polyphenols and antioxidant activity were recorded. Eleven phenolic compounds-including five phenolic acids and six flavonoids-were identified and quantified by high performance liquid chromatography. Ferulic acid and hesperidin were the most abundant compounds whereas caffeic acid was the least abundant phenolic compound in kinnow peel extracts. Maximum inhibition zone was recorded against S. aureus (16.00±0.58 mm) whereas minimum inhibition zone was noted against S. typhimurium (9.00±1.16 mm). It was concluded that kinnow mandarin peels, being a potential source of phenolic compounds with antioxidant and antimicrobial properties, may be used as an ingredient for the preparation of functional foods.

Comparative study of HbA1c and fasting plasma glucose vs the oral glucose tolerance test for diagnosis of diabetes in people with tuberculosis.

AIM: To compare HbA1c and fasting plasma glucose assessment, with the 2-h oral glucose tolerance test as reference, in screening for diabetes in people with turberculosis. METHODS: Individuals (N=268) with newly diagnosed smear-positive tuberculosis were screened for diabetes at a tertiary hospital in Lahore, Pakistan. Diabetes diagnosis was based on WHO criteria: thresholds were ≥48 mmol/mol (≥6.5%) for HbA1c and ≥7.0mmol/l for fasting plasma glucose. RESULTS: The proportion of participants diagnosed with diabetes was 4.9% (n =13) by oral glucose tolerance test, while 11.9% (n =32) and 14.6% (n =39) were diagnosed with diabetes using HbA1c and fasting plasma glucose criteria, respectively. The area under the receiver-operating characteristic curve was 0.79 (95% CI 0.64 to 0.94) for HbA1c and 0.61 (95% CI 0.50 to 0.73) for fasting plasma glucose, with a borderline significant difference between the two tests (P=0.07). CONCLUSIONS: HbA1c and fasting plasma glucose performed equally in terms of diagnosing new diabetes cases in individuals with tuberculosis, but the proportion of participants falsely classified as positive was higher for fasting plasma glucose. This may be explained by acute blood glucose fluctuations when using fasting plasma glucose. HbA1c may be a more reliable test in individuals with transient hyperglycaemia.

Management of bleeding gastric varices: a single session of histoacryl injection may be sufficient.

OBJECTIVE: Gastric variceal bleeding is one of the most feared complications of portal hypertension and hence merits investigation for its optimal therapy. We aimed to evaluate the efficacy and long-term outcome(s) of patients treated with a single session of histoacryl sclerotherapy for active gastric variceal bleeding. METHODS: The medical records of patients who presented with active gastric variceal bleeding between 1998 and 2011 in a tertiary care setting were evaluated retrospectively and the eventual outcome(s) (initial hemostasis, rebleeding, and mortality rate) was assessed at least 1 year after the index bleed. RESULTS: Ninety-seven patients were included. The mean age of the patients was 51.0 ± 12.5 years; 62% were men. Hepatitis C was the most common etiology, found in 63 (65%) patients. The majority of the patients were classified as Child-Pugh grade B and C: 44 (46%) and 29 (31%) patients, respectively. A total of 40 (41%) patients were IGV1, 35 (36%) patients were GOV 2, 20 (21%) patients were GOV 1, and 2 (2%) patients were IGV2. A single session of histoacryl was successful in controlling bleeding in 83 (86%) patients. Seven (7%) patients died during the hospital stay. Rebleeding was observed in 24 (27%) patients during the 1-year follow-up, of whom 12 (50%) were managed successfully with repeated histoacryl injection. The overall mortality rate at 6 weeks, 6 months, and 1 year was 14 (14%), 19 (20%) and 26 (27%) patients, respectively. Child-Pugh classification was a significant prognostic factor of survival (P<0.001). CONCLUSION: A single session of histoacryl sclerotherapy is effective in the majority of patients with active gastric variceal bleeding. Rebleeding was observed in one-fourth of patients, half of whom were controlled successfully by repeated histoacryl sclerotherapy.

Conservative surgery for osteoid osteoma of the lumbar vertebrae.

BACKGROUND: We present two patients with osteoid osteomas of the lumbar spine to highlight the delay in diagnosis and the utility of precise radiological localization enabling tumor resection without jeopardizing spinal stability. CASE DESCRIPTION: Two young patients with refractory back pain presented after having undergone a year of conservative treatment for presumed mechanical back pain. The presence of "red-flag" symptoms (e.g. rest and night pain, and transient pain relief with aspirin) led to the performance of an isotope bone scan, and subsequent computed tomography (CT), which were both consistent with the diagnosis of an osteoid osteoma. After accurate CT-based preoperative planning for tumor excision, a customized conservative surgical technique was utilized that included marginal en-bloc surgical resection of the tumors. As the intervertebral facet joints were also carefully preserved along with stability, no accompanying instrumented fusion was warranted. Both patients returned to full function with complete resolution of their long-standing back pain of more than 2 years. CONCLUSIONS: The diagnosis of osteoid osteoma of the spine requires a high index of clinical suspicion. Diagnostic evaluations should include thin-slice CT scan to assist in planning the most restricted/conservative en-bloc surgical resection while preserving vertebral stability with facet preservation, and thus avoiding instrumented fusions. Without the availability of percutaneous radiofrequency ablation, such restricted/conservative approaches to osteoid osteomas are viable options in countries with developing economies.