Pathologic Findings of Amyloidosis: Recent Advances

Amyloids are aggregations of misfolded protein, which creates fibrillary structures. Unlike normally folded proteins, misfolded fibrils are insoluble and deposited extracellularly or intracellularly. The pathologic mechanism is still unclear, but resultant toxic oligomers within the tissue are known to damage the tissue via aberrant protein interactions. This condition has been known as amyloidosis. Different kinds of amyloid protein may cause similar or different clinical signs and symptoms, largely depending on the target organ it is deposited. However, because treatments and prognoses of each type are different drastically, it is critical to distinguish them and determine the specific type of amyloidosis. The confirmation and typing of amyloid heavily depend on pathologic examination of tissue. The gold standard method for the former is a Congo red staining and birefringence under polarized microscopy. The conventional way for the latter is immunohistochemistry (IHC), where most of the amyloid types can be classified. However, electron microscopy, mass spectrometry, or other molecular methods are required for typing some amyloids that are difficult to identify through IHC. In this chapter, we will describe basic concepts of amyloidosis and pathologic findings of amyloid deposition, including atypical structural deposition. Furthermore, we will review methodologies for amyloid typing briefly

Diagnosis of Amyloidosis: Clinicopathological Advances and Challenges

Amyloidosis is a systemic disease with different subtypes of misfolded, insoluble proteins, which are deposited in viscera and thereby cause damage to the affected organs. Its clinical manifestations are highly variable depending on the organs and tissue affected and often require a high degree of clinical suspicion to achieve correct diagnosis. Development of proteomic tools, radioisotope scintigraphy, immunologic antibody targets by immunohistochemistry, immunofluorescence and microscopic techniques have improved the sensitivity of accurate detection of specific subtypes of amyloid proteins. Newer therapeutic targets have been developed to arrest or suppress the specific types of amyloid proteins, giving rise to the possibility of targeted therapy with better quality of life and improved survival benefits for patients. AL, ATTR, AA and ALECT2 are the major subtypes of amyloidosis and kidney, heart, soft tissue, and peripheral nerves are the most affected viscera. The key to achieving success in better quality of life and overall survival in patients, is in early diagnosis and accurate subtyping of amyloidosis

Tuberculosis among economic migrants: a cross-sectional study of the risk of poor treatment outcomes and impact of a treatment adherence intervention among temporary residents in an urban district in Ho Chi Minh City, Viet Nam.

BACKGROUND Tuberculosis (TB) remains a major cause of avoidable deaths. Economic migrants represent a vulnerable population due to their exposure to medical and social risk factors. These factors expose them to higher risks for TB incidence and poor treatment outcomes. METHODS This cross-sectional study evaluated WHO-defined TB treatment outcomes among economic migrants in an urban district of Ho Chi Minh City, Viet Nam. We measured the association of a patient's government-defined residency status with treatment success and loss to follow-up categories at baseline and performed a comparative interrupted time series (ITS) analysis to assess the impact of community-based adherence support on treatment outcomes. Key measures of interest of the ITS were the differences in step change (β) and post-intervention trend (β). RESULTS Short-term, inter-province migrants experienced lower treatment success (aRR = 0.95 [95% CI: 0.92-0.99], p = 0.010) and higher loss to follow-up (aOR = 1.98 [95% CI: 1.44-2.72], p  55 years of age (aRR = 0.93 [95% CI: 0.89-0.96], p < 0.001), relapse patients (aRR = 0.89 [95% CI: 0.84-0.94], p < 0.001), and retreatment patients (aRR = 0.62 [95% CI: 0.52-0.75], p < 0.001) had lower treatment success rates. TB/HIV co-infection was also associated with lower treatment success (aRR = 0.77 [95% CI: 0.73-0.82], p < 0.001) and higher loss to follow-up (aOR = 2.18 [95% CI: 1.55-3.06], p < 0.001). The provision of treatment adherence support increased treatment success (IRR(β) = 1.07 [95% CI: 1.00, 1.15], p = 0.041) and reduced loss to follow-up (IRR(β) = 0.17 [95% CI: 0.04, 0.69], p = 0.013) in the intervention districts. Loss to follow-up continued to decline throughout the post-implementation period (IRR(β) = 0.90 [95% CI: 0.83, 0.98], p = 0.019). CONCLUSIONS Economic migrants, particularly those crossing provincial borders, have higher risk of poor treatment outcomes and should be prioritized for tailored adherence support. In light of accelerating urbanization in many regions of Asia, implementation trials are needed to inform evidence-based design of strategies for this vulnerable population

A comparative impact evaluation of two human resource models for community-based active tuberculosis case finding in Ho Chi Minh City, Viet Nam

Background: To achieve the WHO End TB Strategy targets, it is necessary to detect and treat more people with active TB early. Scale–up of active case finding (ACF) may be one strategy to achieve that goal. Given human resource constraints in the health systems of most high TB burden countries, volunteer community health workers (CHW) have been widely used to economically scale up TB ACF. However, more evidence is needed on the most cost-effective compensation models for these CHWs and their potential impact on case finding to inform optimal scale-up policies. Methods: We conducted a two-year, controlled intervention study in 12 districts of Ho Chi Minh City, Viet Nam. We engaged CHWs as salaried employees (3 districts) or incentivized volunteers (3 districts) to conduct ACF among contacts of people with TB and urban priority groups. Eligible persons were asked to attend health services for radiographic screening and rapid molecular diagnosis or smear microscopy. Individuals diagnosed with TB were linked to appropriate care. Six districts providing routine NTP care served as control area. We evaluated additional cases notified and conducted comparative interrupted time series (ITS) analyses to assess the impact of ACF by human resource model on TB case notifications. Results: We verbally screened 321,020 persons in the community, of whom 70,439 were eligible for testing and 1138 of them started TB treatment. ACF activities resulted in a + 15.9% [95% CI: + 15.0%, + 16.7%] rise in All Forms TB notifications in the intervention areas compared to control areas. The ITS analyses detected significant positive post-intervention trend differences in All Forms TB notification rates between the intervention and control areas (p = 0.001), as well as between the employee and volunteer human resource models (p = 0.021). Conclusions: Both salaried and volunteer CHW human resource models demonstrated additionality in case notifications compared to routine case finding by the government TB program. The salaried employee CHW model achieved a greater impact on notifications and should be prioritized for scale-up, given sufficient resources

Discorvery of Entomopathogenic fungi Cordyceps takaomontana at Langbian Mountain, Lam Dong, Vietnam

The stromata of Cordyceps takaomontana Y. Kobayashi (1941) were found on the Langbian Mountain, Da Lat, Vietnam at the height of 1.650 meter above sea level, on the larva of Lepidoptera. Stromata were lemon-yellow, clavate to enlongated clavate, arising from a white pseudosclerotium. The fertile head was on the top part of stromata, darker colored in comparison to the stipe. Perithecium was narrowly ovoid, superficial and forming dark yellow punctate on the surface of stromata. Ascus was cylindrical with semi-spherical cap. Ascospores were cylindrical, truncated and separately after discharge from the ascus. Pure culture was isolated on Potato Glucose Agar (PGA) medium: white colony in young and yellow in old. The isolated mycelium was not homogenous in thickness and in growth rate at the peripheral area. Conidiophores were phialide, tapering to both apexes. Conidia had elliptical shape and formed into chains after maturation. DNA was isolated, then purified from pure mycelium and used to amplifying the nrLSU (nuclear ribosomal large subunit) and rpb1 (RNA polymerase II largest subunit) genes. The amplified products were used for sequencing, proof-reading by some professional softwares before combining with other nrLSU and rpb1 sequences. Then this database was used to search for the suitable evolution model as well as to construct the phylogenetic trees. The results of phylogenetic analysis completely supported the morphological classification: DL0038A and DL0038B were Cordyceps takaomontana Y. Kobayashi (1941)

Assessment of Water Quality During 2018-2022 in the Vam Co River Basin, Vietnam

Water pollution in the Vam Co River basin is becoming more complicated due to untreated wastewater being directly discharged into rivers and canals from agricultural, industrial, and domestic activities. To assess the water quality in this area, this study conducted monitoring at ten sampling locations (S1-S10) from 2018 to 2022, calculated the Water Quality Index (WQI) for each parameter, and simulated water quality in 2022 using the 1D- MIKE 11 model developed by DHI with two main modules including HD and AD. The findings showed that most parameters did not surpass the allowable limits per QCVN 08-MT:2015/BTNMT on Vietnam National Technical Regulation on Surface Water Quality. However, organic and microbial pollution led to certain parameters, such as BOD5, COD, and Coliform, exceeding the limits. The lowest water quality was recorded in Long An province, especially at sampling locations S3, S4, and S6, with the average WQI for nine water quality parameters from February to July 2022 being 58.4, 67.8, and 21.1, respectively. Additionally, the simulation outcomes of the MIKE 11 model salinity, BOD5, DO, and NH4 aligned with the real measurements taken. It has been observed that the southern area of the Vam Co River Basin possesses poorer water quality than the northern part, with Long An province located downstream of the Vam Co River basin being the primary source of pollution. The development of this hydraulic model signifies a crucial milestone in comprehending and regulating the effects of pollution in monitoring and managing water management systems, controlling saline intrusion, and ensuring water supply for agricultural production and daily use in the Vam Co River basin

Evaluating the yield of systematic screening for tuberculosis among three priority groups in Ho Chi Minh City, Viet Nam.

BACKGROUND In order to end tuberculosis (TB), it is necessary to expand coverage of TB care services, including systematic screening initiatives. However, more evidence is needed for groups among whom systematic screening is only conditionally recommended by the World Health Organization. This study evaluated concurrent screening in multiple target groups using community health workers (CHW). METHODS In our two-year intervention study lasting from October 2017 to September 2019, CHWs in six districts of Ho Chi Minh City, Viet Nam verbally screened three urban priority groups: (1) household TB contacts; (2) close TB contacts; and (3) residents of urban priority areas without clear documented exposure to TB including hotspots, boarding homes and urban slums. Eligible persons were referred for further screening with chest radiography and follow-on testing with the Xpert MTB/RIF assay. Symptomatic individuals with normal or without radiography results were tested on smear microscopy. We described the TB care cascade and characteristics for each priority group, and calculated yield and number needed to screen. Subsequently, we fitted a mixed-effect logistic regression to identify the association of these target groups and secondary patient covariates with TB treatment initiation. RESULTS We verbally screened 321 020 people including 24 232 household contacts, 3182 social and close contacts and 293 606 residents of urban priority areas. This resulted in 1138 persons treated for TB, of whom 85 were household contacts, 39 were close contacts and 1014 belonged to urban priority area residents. The yield of active TB in these groups was 351, 1226 and 345 per 100 000, respectively, corresponding to numbers needed to screen of 285, 82 and 290. The fitted model showed that close contacts [adjusted odds ratio (aOR) = 2.07; 95% CI: 1.38-3.11; P < 0.001] and urban priority area residents (aOR = 2.18; 95% CI: 1.69-2.79; P < 0.001) had a greater risk of active TB than household contacts. CONCLUSIONS The study detected a large number of unreached persons with TB, but most of them were not among persons in contact with an index patient. Therefore, while programs should continue to optimize screening in contacts, to close the detection gap in high TB burden settings such as Viet Nam, coverage must be expanded to persons without documented exposure such as residents in hotspots, boarding homes and urban slums

An Evaluation of Programmatic Community-Based Chest X-ray Screening for Tuberculosis in Ho Chi Minh City, Vietnam.

Across Asia, a large proportion of people with tuberculosis (TB) do not report symptoms, have mild symptoms or only experience symptoms for a short duration. These individuals may not seek care at health facilities or may be missed by symptom screening, resulting in sustained TB transmission in the community. We evaluated the yields of TB from 114 days of community-based, mobile chest X-ray (CXR) screening. The yields at each step of the TB screening cascade were tabulated and we compared cohorts of participants who reported having a prolonged cough and those reporting no cough or one of short duration. We estimated the marginal yields of TB using different diagnostic algorithms and calculated the relative diagnostic costs and cost per case for each algorithm. A total of 34,529 participants were screened by CXR, detecting 256 people with Xpert-positive TB. Only 50% of those diagnosed with TB were detected among participants reporting a prolonged cough. The study's screening algorithm detected almost 4 times as much TB as the National TB Program's standard diagnostic algorithm. Community-based, mobile chest X-ray screening can be a high yielding strategy which is able to identify people with TB who would likely otherwise have been missed by existing health services

Delphi:A Democratic and Cost-Effective Method of Consensus Generation in Transplantation

The Thrombotic Microangiopathy Banff Working Group (TMA-BWG) was formed in 2015 to survey current practices and develop minimum diagnostic criteria (MDC) for renal transplant TMA (Tx-TMA). To generate consensus among pathologists and nephrologists, the TMA BWG designed a 3-Phase study. Phase I of the study is presented here. Using the Delphi methodology, 23 panelists with &gt;3 years of diagnostic experience with Tx-TMA pathology listed their MDC suggesting light, immunofluorescence, and electron microscopy lesions, clinical and laboratory information, and differential diagnoses. Nine rounds (R) of consensus resulted in MDC validated during two Rs using online evaluation of whole slide digital images of 37 biopsies (28 TMA, 9 non-TMA). Starting with 338 criteria the process resulted in 24 criteria and 8 differential diagnoses including 18 pathologic, 2 clinical, and 4 laboratory criteria. Results show that 3/4 of the panelists agreed on the diagnosis of 3/4 of cases. The process also allowed definition refinement for 4 light and 4 electron microscopy lesions. For the first time in Banff classification, the Delphi methodology was used to generate consensus. The study shows that Delphi is a democratic and cost-effective method allowing rapid consensus generation among numerous physicians dealing with large number of criteria in transplantation.</p

Optimising diagnosis and treatment of tuberculosis infection in community and primary care settings in two urban provinces of Viet Nam: a cohort study

Objectives: To end tuberculosis (TB), the vast reservoir of 1.7–2.3 billion TB infections (TBIs) must be addressed, but achieving global TB preventive therapy (TPT) targets seems unlikely. This study assessed the feasibility of using interferon-γ release assays (IGRAs) at lower healthcare levels and the comparative performance of 3-month and 9-month daily TPT regimens (3HR/9H). Design, setting, participants and intervention: This cohort study was implemented in two provinces of Viet Nam from May 2019 to September 2020. Participants included household contacts (HHCs), vulnerable community members and healthcare workers (HCWs) recruited at community-based TB screening events or HHC investigations at primary care centres, who were followed up throughout TPT. Primary and secondary outcomes: We constructed TBI care cascades describing indeterminate and positivity rates to assess feasibility, and initiation and completion rates to assess performance. We fitted mixed-effects logistic and stratified Cox models to identify factors associated with IGRA positivity and loss to follow-up (LTFU). Results: Among 5837 participants, the indeterminate rate was 0.8%, and 30.7% were IGRA positive. TPT initiation and completion rates were 63.3% (3HR=61.2% vs 9H=63.6%; p=0.147) and 80.6% (3HR=85.7% vs 9H=80.0%; p=0.522), respectively. Being male (adjusted OR=1.51; 95% CI: 1.28 to 1.78; p<0.001), aged 45–59 years (1.30; 1.05 to 1.60; p=0.018) and exhibiting TB-related abnormalities on X-ray (2.23; 1.38 to 3.61; p=0.001) were associated with positive IGRA results. Risk of IGRA positivity was lower in periurban districts (0.55; 0.36 to 0.85; p=0.007), aged <15 years (0.18; 0.13 to 0.26; p<0.001), aged 15–29 years (0.56; 0.42 to 0.75; p<0.001) and HCWs (0.34; 0.24 to 0.48; p<0.001). The 3HR regimen (adjusted HR=3.83; 1.49 to 9.84; p=0.005) and HCWs (1.38; 1.25 to 1.53; p<0.001) showed higher hazards of LTFU. Conclusion: Providing IGRAs at lower healthcare levels is feasible and along with shorter regimens may expand access and uptake towards meeting TPT targets, but scale-up may require complementary advocacy and education for beneficiaries and providers