Portable, handheld, and affordable blood perfusion imager for screening of subsurface cancer in resource-limited settings.

Precise information on localized variations in blood circulation holds the key for noninvasive diagnostics and therapeutic assessment of various forms of cancer. While thermal imaging by itself may provide significant insights on the combined implications of the relevant physiological parameters, viz. local blood perfusion and metabolic balance due to active tumors as well as the ambient conditions, knowledge of the tissue surface temperature alone may be somewhat inadequate in distinguishing between some ambiguous manifestations of precancer and cancerous lesions, resulting in compromise of the selectivity in detection. This, along with the lack of availability of a user-friendly and inexpensive portable device for thermal-image acquisition, blood perfusion mapping, and data integration acts as a deterrent against the emergence of an inexpensive, contact-free, and accurate in situ screening and diagnostic approach for cancer detection and management. Circumventing these constraints, here we report a portable noninvasive blood perfusion imager augmented with machine learning-based quantitative analytics for screening precancerous and cancerous traits in oral lesions, by probing the localized alterations in microcirculation. With a proven overall sensitivity >96.66% and specificity of 100% as compared to gold-standard biopsy-based tests, the method successfully classified oral cancer and precancer in a resource-limited clinical setting in a double-blinded patient trial and exhibited favorable predictive capabilities considering other complementary modes of medical image analysis as well. The method holds further potential to achieve contrast-free, accurate, and low-cost diagnosis of abnormal microvascular physiology and other clinically vulnerable conditions, when interpreted along with complementary clinically evidenced decision-making perspectives.

Performance of visual inspection, partial genotyping, and their combination for the triage of women living with HIV who are screen positive for human papillomavirus: Results from the AIMA-CC ANRS 12375 multicentric screening study.

The WHO recommends the use of human papillomavirus (HPV) testing for primary cervical cancer (CC) screening because of its high sensitivity. However, triage is desirable to correctly identify HPV+ women who have high-grade lesions (CIN2+) and require treatment. The ANRS-12375 study was conducted in Côte d'Ivoire, Burkina Faso and Cambodia to assess the performance, feasibility and benefits of different triage options for detecting CIN2+ lesions: partial (HPV16 and HPV16/18/45) and extended genotyping, visual inspection (VIA) alone and VIA combined with partial genotyping. VIA was performed by gynecologists. The sensitivity, specificity, and diagnostic likelihood ratio (DLR) of each triage option for detecting CIN2+ lesions with histology as a reference standard were calculated. Of the 2253 women living with HIV (WLHIV) included, 932 (41%) were HPV+. A CIN2+ lesion was identified in 105 (13%) of the 777 participants with histopathology results. The sensitivity of VIA as a triage test for CIN2+ patients was 89%, while that for extended genotyping was 89%, that for HPV16/18/45 partial genotyping was 51%, and that for HPV16 partial genotyping was 36%. The specificities for these tests were 45%, 29%, 72%., and 85%, respectively. Combining VIA and/or partial genotyping positivity slightly increased the sensitivity (94%) at the cost of lower specificity (28%). There was significant intersite heterogeneity (p = .04). Among the three triage tests with a sensitivity ≥85%, the VIA had the highest specificity and positive likelihood ratio (p < .001). VIA and extended genotyping, whether independent or combined, are good triage options with high sensitivity for identifying WLHIV needing treatment for CIN2+.

Setting up a state-of-the-art laboratory in resource limited settings: A case study of the biomedical science research and training centre in Northeast Nigeria.

African science has substantial potential, yet it grapples with significant challenges. Here we describe the establishment of the Biomedical Science Research and Training Centre (BioRTC) in Yobe State, Northeast Nigeria, as a case study of a hub fostering on-continent research and describe strategies to overcome current barriers. We detail the steps taken to establish BioRTC, emphasising the critical importance of stakeholder engagement, community involvement, resource optimisation and collaborations. With its state-of-the-art facilities and commitment to training African scientists, BioRTC is poised to significantly advance neuroscience research and training in the region. Although we are in the early stages of our journey, our model, emphasizing open access and inclusivity, offers a replicable blueprint for neuroscience research development in similar resource-limited settings, promising to enrich the global neuroscience community. We invite the support and collaboration of those who share our vision and believe in our potential.

A Machine Learning Algorithm Avoids Unnecessary Paracentesis for Exclusion of SBP in Cirrhosis in Resource-limited Settings.

BACKGROUND & AIMS: Despite the poor prognosis associated with missed or delayed spontaneous bacterial peritonitis (SBP) diagnosis, <15% get timely paracentesis, which persists despite guidelines/education in the United States. Measures to exclude SBP non-invasively where timely paracentesis cannot be performed could streamline this burden. METHODS: Using Veterans Health Administration Corporate Data Warehouse (VHA-CDW) we included patients with cirrhosis between 2009 and 2019 who underwent timely paracentesis and collected relevant clinical information (demographics, cirrhosis severity, medications, vitals, and comorbidities). XGBoost-models were trained on 75% of the primary cohort, with 25% reserved for testing. The final model was further validated in 2 cohorts: Validation cohort #1: In VHA-CDW, those without prior SBP who received 2nd early paracentesis, and Validation cohort #2: Prospective data from 276 non-electively admitted University hospital patients. RESULTS: Negative predictive values (NPVs) at 5%,10%, and 15% probability cutoffs were examined. Primary cohort: n = 9643 (mean age, 63.1 ± 8.7 years; 97.2% men; SBP, 15.0%) received first early paracentesis. Testing-set NPVs for SBP were 96.5%, 93.0%, and 91.6% at the 5%, 10%, and 15% probability thresholds, respectively. In Validation cohort #1: n = 2844 (mean age, 63.14 ± 8.37 years; 97.1% male; SBP, 9.7%) with NPVs were 98.8%, 95.3%, and 94.5%. In Validation cohort #2: n = 276 (mean age, 56.08 ± 9.09; 59.6% male; SBP, 7.6%) with NPVs were 100%, 98.9%, and 98.0% The final machine learning model showed the greatest net benefit on decision-curve analyses. CONCLUSIONS: A machine learning model generated using routinely collected variables excluded SBP with high NPV. Applying this model could ease the need to provide paracentesis in resource-limited settings by excluding those unlikely to have SBP.

Development of RPA-Cas12a assay for rapid and sensitive detection of Pneumocystis jirovecii.

Pneumocystis jirovecii is a prevalent opportunistic fungal pathogen that can lead to life-threatening Pneumocystis pneumonia in immunocompromised individuals. Given that timely and accurate diagnosis is essential for initiating prompt treatment and enhancing patient outcomes, it is vital to develop a rapid, simple, and sensitive method for P. jirovecii detection. Herein, we exploited a novel detection method for P. jirovecii by combining recombinase polymerase amplification (RPA) of nucleic acids isothermal amplification and the trans cleavage activity of Cas12a. The factors influencing the efficiency of RPA and Cas12a-mediated trans cleavage reaction, such as RPA primer, crRNA, the ratio of crRNA to Cas12a and ssDNA reporter concentration, were optimized. Our RPA-Cas12a-based fluorescent assay can be completed within  30-40 min, comprising a 25-30 min RPA reaction and a 5-10 min trans cleavage reaction. It can achieve a lower detection threshold of 0.5 copies/µL of target DNA with high specificity. Moreover, our RPA-Cas12a-based fluorescent method was examined using 30 artificial samples and demonstrated high accuracy with a diagnostic accuracy of 93.33%. In conclusion, a novel, rapid, sensitive, and cost-effective RPA-Cas12a-based detection method was developed and demonstrates significant potential for on-site detection of P. jirovecii in resource-limited settings.

The management of osteosarcoma in children and adolescents in a resource-limited setting: quality improvement considerations to improve treatment outcomes.

BACKGROUND: The survival rates for children and adolescents with osteosarcoma in low-income countries are poor. Insufficient data regarding the challenges of managing osteosarcoma in resource-limited settings has been published. We evaluated the treatment of osteosarcoma in children and adolescents with the aim of improving the health system and management outcomes. METHODS: We sourced data on children under 18 years treated for osteosarcoma at the Uganda Cancer Institute between January 2016 and December 2020. Descriptive statistics and Kaplan-Meier survival analysis were used. RESULTS: Seventy-four osteosarcoma cases were identified, with a median age of 13 years (IQR 9.8-15). Referrals were made after a median of 28 days (range 1-147). Before appropriate referral, more than a quarter (26%) had undergone invasive procedures that could compromise tumour integrity and outcome. Half (50%) of the patients had metastatic disease at diagnosis, primarily to the lungs (n = 43; 92%). Only 14 (33%) patients received neoadjuvant chemotherapy. Forty-three (58.1%) patients underwent limb amputation surgery, including 25 localized tumours and 18 patients with distant metastatic disease. No metastatectomies were performed. Adjuvant chemotherapy was delayed for longer than 21 days in 26 (61%) patients. No pathology reports described the status of resection margins or the degree of chemotherapy-induced necrosis. Twenty-six (35%) patients abandoned treatment, mainly due to pending radical surgery (n = 18/26; 69%). Only 18% (n = 13) were still alive; 46% (n = 34) had died; and 37% (n = 27) had an unknown status. The median overall survival was 1.1 years, and was significantly negatively affected by disease metastasis, timing of adjuvant therapy, and treatment abandonment. CONCLUSIONS: Osteosarcoma outcomes for children and adolescents at the Uganda Cancer Institute are extremely poor. The quality of care can be improved by addressing delayed referrals, high rates of prior manipulative therapy, metastatic disease, treatment abandonment, surgical challenges, and delayed resumption of adjuvant chemotherapy.

Smartphone-driven centrifugal microfluidics for diagnostics in resource limited settings.

The broad availability of smartphones has provided new opportunities to develop less expensive, portable, and integrated point-of-care (POC) platforms. Here, a platform that consists of three main components is introduced: a portable housing, a centrifugal microfluidic disc, and a mobile phone. The mobile phone supplies the electrical power and serves as an analysing system. The low-cost housing made from cardboard serves as a platform to conduct tests. The electrical energy stored in mobile phones was demonstrated to be adequate for spinning a centrifugal disc up to 3000 revolutions per minute (RPM), a rotation speed suitable for majority of centrifugal microfluidics-based assays. For controlling the rotational speed, a combination of magnetic and acoustic tachometry using embedded sensors of the mobile phone was used. Experimentally, the smartphone-based tachometry was proven to be comparable with a standard laser-based tachometer. As a proof of concept, two applications were demonstrated using the portable platform: a colorimetric sandwich immunoassay to detect interleukin-2 (IL-2) having a limit of detection (LOD) of 65.17 ng/mL and a fully automated measurement of hematocrit level integrating blood-plasma separation, imaging, and image analysis that takes less than 5 mins to complete. The low-cost platform weighing less than 150 g and operated by a mobile phone has the potential to meet the REASSURED criteria for advanced diagnostics in resource limited settings.

Interests and Barriers to Medical Students Participation in a Dedicated Global Surgery Curriculum.

INTRODUCTION: Despite many institutions establishing global surgery (GS) programs to support clinical care and education in resource-limited settings, few have established a specific curriculum in GS. This study's objective was to assess medical student interest in such a curriculum and prospects for future careers in GS/global health (GH), and to define the barriers to pursuing an international rotation. METHODS: We conducted an anonymous online survey of all 495 medical students at a major academic medical center in the mid-South that collected demographic data, country of origin, interest in a GS/GH elective, and barriers to pursuing a GS/GH rotation abroad. The data were analyzed using SPSS software. RESULTS: Prior international experience increased the likelihood of a student's involvement in GS/GH and more preclinical (years 1 & 2) students (90%) than clinical students. (years 3 & 4) (70%) felt strongly about the value of a GS/GH experience. Of the 163 students who completed the survey, 80% expressed interest in a GS/GH elective, with preclinical students expressing more interest (90%) than clinical students (71%). This interest strongly correlated with an interest in pursuing a career in GH (94%) and/or GS (100%). Identified barriers to engagement in a GS/GH experience abroad included financing (74%), scheduling (58%), family obligations (23%), and personal safety (19%). CONCLUSIONS: The students we surveyed were very interested in a GS/GH curriculum that included a rotation abroad, especially if they were to receive financial support. Preclinical students expressed more willingness to self-fund such experiences. The findings of this survey further strengthen the need to incorporate GS/GH in medical school curricula.

Management of disseminated histoplasmosis in a high-complexity clinic in Cali, Colombia.

Histoplasmosis presents a substantial clinical challenge globally, with a particular prevalence in South America, especially among patients with concurrent Human Immunodeficiency Virus (HIV) infection. Despite itraconazole's established efficacy, investigating alternative therapeutic approaches remains imperative. This is the largest study in our region to date, assessing the effectiveness of the less explored posaconazole treatment. This observational study, conducted at Fundación Valle del Lili (FVL) from 2016 to 2022, encompassed adults with disseminated histoplasmosis. Patients (n = 31) were treated with liposomal amphotericin B as an initial treatment, followed by consolidation treatment with posaconazole or itraconazole. Patients with single-organ cases, those lacking microbiological diagnosis, those who received initial treatment with antifungals other than liposomal Amphotericin B and those with < 6 months follow-up were excluded (Figure 1). Analyses considered population characteristics, treatments, and outcomes. Patients (average age: 45.6; 58.1% female) had common comorbidities (HIV 38.7%, solid organ transplantation 29% and oncologic disease 12.9%). Lungs (48.4%) and lymph nodes (16.1%) were commonly affected. Biopsy (64.5%) was the primary diagnostic method. Initial treatment with liposomal amphotericin B (100%) was given for 14 days on average. Follow-up indicated 71% completion with 19.4% requiring treatment modifications. Notably, 70.9% completed a posaconazole consolidation regimen over 350 days on average. Drug interactions during consolidation (80.6%) were common. No relapses occurred, and three deaths unrelated to histoplasmosis were reported. Traditionally, itraconazole has been the prevalent initial treatment; however, in our cohort, 55.9% of patients received posaconazole as the primary option. Encouragingly, posaconazole showed favorable tolerance and infection resolution, suggesting its potential as an effective and well-tolerated alternative for consolidation treatment. This finding prompts further exploration of posaconazole, potentially leading to more effective patient care and better outcomes.

Histoplasmosis is a critical concern in South America, notably among human immunodeficiency virus patients, leading to high mortality rates. This study, the largest in our region, investigates the effectiveness of posaconazole as an alternative treatment to itraconazole. The results offer the potential for enhanced patient care and improved outcomes.

Effectiveness of a Wilms tumour treatment guideline adapted to local circumstances in sub-Saharan Africa: A report from Wilms Africa Phase II-CANCaRe Africa.

BACKGROUND: Wilms tumour (WT) is one of the cancer types targeted by the Global Initiative for Childhood Cancer (GICC). The objective of this study was to describe the outcomes of Wilms Africa Phase II in sub-Saharan Africa. METHODS: Wilms Africa Phase II used a comprehensive WT treatment protocol in a multi-centre, prospective study conducted in eight hospitals in Ethiopia (2), Ghana (2), Malawi, Cameroon, Zimbabwe and Uganda. Eligibility criteria were: age younger than 16 years, unilateral WT, diagnosed between 1 January 2021 and 31 December 2022. RESULTS: We included 230 WT patients, median age 3 years, 53% male. Median maximum tumour diameter at diagnosis was 13.6 cm and 33% of patients had metastatic disease. Nephrectomy was performed in 71% of patients, of whom 21% had a tumour rupture. Two-year event-free survival (EFS) was 41.3% ± 3.9% after a median follow-up of 17 months (range: 1-33 months), with treatment abandonment considered an event. Treatment abandonment occurred in 26% and death during treatment in 14%. Disease relapse occurred in 10%. Two-year EFS of the 26 patients who received radiotherapy was 64.5% ± 9.7% with no reported disease relapse. CONCLUSION: Patients continue to present late with advanced WT in sub-Saharan Africa, and their survival is below the 60% GICC target. Prevention of treatment abandonment and treatment-related mortality remain important. Earlier diagnosis and access to radiotherapy are expected to decrease disease-related mortality.

Surgical aspects and outcomes after nephrectomy for Wilms tumour in sub-Saharan Africa: A report from Wilms Africa Phase II-CANCaRe Africa.

BACKGROUND: Wilms tumour (WT) is one of the common and curable cancer types targeted by the Global Initiative for Childhood Cancer. Tumour excision is essential for cure. This analysis focuses on surgical outcomes of patients with WT in sub-Saharan Africa. METHODS: We implemented a risk-stratified WT treatment guideline as a multicentre, prospective study across eight hospitals and six countries. Eligibility criteria were age 6 months to 16 years, unilateral WT, surgery performed after preoperative chemotherapy and diagnosed between 1 January 2021 and 31 December 2022. Data collection included a specific surgical case report form (CRF). RESULTS: The study registered 230 patients, among whom 164 (71.3%) had a nephrectomy. Ninety-eight percent of patients had a completed surgical CRF. Out 164 patients, 50 (30.5%) had distant metastases. Median tumour diameter at surgery was 11.0 cm. Lymph node sampling was done in 122 (74.3%) patients, 34 (20.7%) had intraoperative tumour rupture, and for 18 (10.9%), tumour resection involved en bloc resection of another organ. Tumour size at surgery was significantly correlated with tumour rupture (p < .01). With a median follow-up of 17 months (range: 2-33), 23 (14.0%) patients have relapsed. Twenty-two (13.4%) patients abandoned treatment post nephrectomy. Two-year event-free survival was 60.4% ± 4.7% with treatment abandonment as an event. CONCLUSION: Survival post nephrectomy is challenged by treatment abandonment, treatment-related mortality and relapse. Large tumours after preoperative chemotherapy were associated with a higher risk of tumour rupture. Earlier diagnosis and access to radiotherapy are expected to improve survival.

Reflections on 20 years of the Wilms Africa project: Lessons learned and the way forward.

Wilms tumour (WT) is one of the common and curable childhood cancer types included in the Global Initiative for Childhood Cancer (GICC) to monitor progress. Local evidence is key to finding effective and sustainable solutions to local challenges to improve care and survival. Local evidence generated by the Wilms Africa project is summarised with recommendations for the future.

Prevention of treatment abandonment remains an important challenge to increase survival of Wilms tumor in sub-Saharan Africa: A report from Wilms Africa-CANCaRe Africa.

BACKGROUND: The Wilms Africa studies implemented an adapted Wilm's tumor (WT) treatment protocol in sub-Saharan Africa in two phases. Phase I began with four sites and provided out-of-pocket costs. Phase II expanded the number of sites, but lost funding provision. Objective is to describe the outcomes of Phase II and compare with Phase I. METHODS: Wilms Africa Phase I (n = 4 sites; 2014-2018) and Phase II (n = 8 sites; 2021-2022) used adapted treatment protocols. Funding for families' out-of-pocket costs was provided during Phase I but not Phase II. Eligibility criteria were age less than 16 years and newly diagnosed unilateral WT. We documented patients' outcome at the end of planned first-line treatment categorized as treatment abandonment, death during treatment, and disease-related events (death before treatment, persistent disease, relapse, or progressive disease). Sensitivity analysis compared outcomes in the same four sites. RESULTS: We included 431 patients in Phase I (n = 201) and Phase II (n = 230). The proportion alive without evidence of disease decreased from 69% in Phase I to 54% in Phase II at all sites (p = .002) and 58% at the original four sites (p = .04). Treatment abandonment increased overall from 12% to 26% (p < .001), and was 20% (p = .04) at the original four sites. Disease-related events (5% vs. 6% vs. 6%) and deaths during treatment (14% vs. 14% vs. 17%) were similar. CONCLUSION: Provision of out-of-pocket costs was important to improve patient outcomes at the end of planned first-line treatment in WT. Prevention of treatment abandonment remains an important challenge.

Local evidence in sub-Saharan Africa; the CANCaRe Africa experience-Lessons learned and shared thoughts about the way forward.

Collaborative research generating local evidence is key to closing the research and survival gap between sub-Saharan Africa and high-income countries. Lessons learned by CANCaRe Africa, the Collaborative African Network for Childhood Cancer Care and Research while pioneering such research are being discussed together with recommendations for the future.

Clinical characteristics and management of liver abscess in The Gambia, a resource-limited country.

Liver abscess is endemic in resource-limited countries such as The Gambia where access to advanced imaging techniques or modern treatment modalities is limited. Despite this, mortality in this cohort was low. Therefore antibiotic therapy combined with percutaneous abscess drainage remains a reasonable treatment strategy of liver abscess in resource-poor settings.

Predictors of complications and mortality among patients undergoing pacemaker implantation in resource-limited settings: a 10-year retrospective follow-up study.

INTRODUCTION: Pacemakers (PMs) are used to treat patients with severe bradycardia symptoms. They do, however, pose several complications. Even with these risks, there are only a few studies assessing PM implantation outcomes in resource-limited settings like Ethiopia and other sub-Saharan countries in general. Therefore, this study aims to assess the mid-term outcome of PM implantation in patients who have undergone PM implantation in the Cardiac Center of Ethiopia by identifying the rate and predictors of complications and death. METHODOLOGY: This retrospective study was conducted at the Cardiac Center of Ethiopia from October 2023 to January 2024 on patients who had PM implantation from September 2012 to August 2023 to assess the midterm outcome of the patients. Complication rate and all-cause mortality rate were the outcomes of our study. Multivariable logistic regression was used to identify factors associated with complications and death. To analyze survival times, a Kaplan-Meier analysis was performed. RESULTS: This retrospective follow-up study included 182 patients who underwent PM implantation between September 2012 and August 2023 and were at least 18 years old. The patients' median follow-up duration was 72 months (Interquartile range (IQR): 36-96 months). At the end of the study, 26.4% of patients experienced complications. The three most frequent complications were lead dislodgement, which affected 6.6% of patients, PM-induced tachycardia, which affected 5.5% of patients, and early battery depletion, which affected 5.5% of patients. Older age (Adjusted Odds Ratio (AOR) 1.1, 95% CI 1.04-1.1, p value < 0.001), being female (AOR 4.5, 95%CI 2-9.9, p value < 0.001), having dual chamber PM (AOR 2.95, 95%CI 1.14-7.6, p value = 0.006) were predictors of complications. Thirty-one (17%) patients died during the follow-up period. The survival rates of our patients at 3, 5, and 10 years were 94.4%, 92.1%, and 65.5% respectively with a median survival time of 11 years. Patients with a higher Charlson comorbidity index before PM implantation (AOR 1.2, 95% CI 1.1-1.8, p = 0.04), presence of complications (AOR 3.5, 95% CI 1.2-10.6, p < 0.03), and New York Heart Association (NYHA) class III or IV (AOR 3.3, 95% CI 1.05-10.1, p = 0.04) were associated with mortality. CONCLUSION: Many complications were experienced by patients who had PMs implanted, and several factors affected their prognosis. Thus, it is essential to identify predictors of both complications and mortality to prioritize and address the manageable factors associated with both mortality and complications.

Clinical competency of nurses trained in competency-based versus objective-based education in the Democratic Republic of the Congo: a qualitative study.

BACKGROUND: Designing competency-based education (CBE) programmes is a priority in global nursing education for better nursing care for the population. In the Democratic Republic of the Congo (DRC), object-based education (OBE) remains mainstream in pre-service nursing education programmes. Recently, the Ministry of Health developed a self-assessment tool and quantitatively compared the clinical competency of CBE- and OBE-trained nurses. This study aimed to qualitatively triangulate the results of self-evaluation by exploring perception of supervisors, incumbent CBE-, and OBE-trained nurses in comparison with the competence of the two types of nurses, and to identify influential factors or barriers to their competence in clinical settings. METHODS: A qualitative descriptive approach with conventional content analysis was applied. Twenty interviews with clinical supervisors who oversaw both CBE- and OBE-trained nurses, 22 focus group discussions (FGDs) with CBE-trained nurses, and 21 FGDs with OBA-trained nurses currently working in health facilities were conducted. Participants of the FGDs were selected from the participants of the DRC self-assessment competency comparison study where there was no statistically significance between CBE- and OBE-trained nurses in the demographic characteristics. Data were analysed in terms of the competencies identified by the Ministry of Health. RESULTS: The supervisors recognised that the CBE-trained nurses had stronger competencies in professional communication, making decisions about health problems, and engaging in professional development, but were weak in clinical skills. This study identified challenges for supervisors in assuring standardised care in health facilities with OBE- and CBE-trained nurses, as well as barriers for CBE-trained nurses as a minority in the workplace in demonstrating their competencies. CONCLUSIONS: The study results support the Ministry of Health's policy to expand CBE in pre-service education programmes but reveal that its slow implementation impedes full utilisation of the acquired competencies at health facilities. Implementation could be accelerated by strengthening cooperation among the Ministry of Health's three human resource departments, and developing and implementing a well-planned, legally binding, long-term CBE reform strategy, including an approach to the Continuing Professional Development system.

Characteristics and outcome of pregnancy-related acute kidney injury in a teaching hospital in a low-resource setting: a five-year retrospective review.

BACKGROUND: Pregnancy-related kidney injury contributes to a high burden of acute kidney injury in low-resource settings and causes maternal and perinatal morbidity and mortality. Few studies have examined the impact of acute kidney injury in resource-limited countries, with very limited research on pregnancy-specific disorders in Ethiopia. This study aimed to determine the characteristics of pregnancy-related acute kidney injury, outcomes and associated factors. METHODS: A retrospective study was conducted to evaluate the clinical profile and maternal-fetal outcome of pregnancy-related acute kidney injury at Ayder Comprehensive Specialized Hospital in Tigray, Ethiopia, from January 1, 2017, to December 31, 2021. Maternal and fetal outcomes were analyzed using descriptive statistics. Multivariate logistic regression was used to determine the association between the dependent and independent variables. RESULTS: Of 27,350 mothers who delivered at Ayder Comprehensive Specialized Hospital between January 1, 2017, and December 31, 2021, a total of 187 women developed pregnancy-related acute kidney injury, a prevalence rate of 68 per 100,000 births. Preeclampsia, sepsis and pre-renal causes due to dehydration and hemorrhage were the most common causes of pregnancy-related acute kidney injury in this study. Hemodialysis was needed in 8.6% (n = 16) of patients. Of the 187 pregnancy-related acute kidney injuries, 143 (76.5%) recovered completely and 30 (16%) partially. The mortality rate was 7.5%. Preexisting chronic kidney disease (AOR = 30.13; 95% CI: 2.92, 310.84), use of vasoactive agents (AOR = 5.77; 95% CI: 1.47, 22.67), increase in creatinine per unit (AOR = 1.65; 95% CI: 1.11, 2.45) and complications related to acute kidney injury (AOR = 5.26; 95% CI: 1.73, 16.00) were determinants of the composite endpoints (partial renal recovery and death). CONCLUSIONS: This study emphasizes acute kidney injury in resource-limited settings is a significant cause of maternal and fetal morbidity and mortality. The vast majority of patients with pregnancy-related acute kidney injury recovered completely from kidney injury. The main causes of pregnancy-related acute kidney injury were preeclampsia, sepsis and pre-renal associated with hemorrhage and dehydration. Preexisting renal disease, use of vasopressors, increase in creatinine per unit and complications associated with acute kidney injury were determining factors for concomitant fetomaternal mortality. Appropriate preventive strategies during prenatal care and prompt treatment are needed for pregnancy-related acute kidney injury.

Integrated assessment of malignancy in IDH-mutant astrocytoma with p16 and methylthioadenosine phosphorylase immunohistochemistry.

In the fifth edition of the World Health Organization's (WHO) classification of tumors of the central nervous system (CNS), molecular analysis is required for not only determining each tumor type but assessing its prognosis based on malignancy (CNS WHO grade). A notable example is the loss of tumor suppressor gene cyclin-dependent kinase inhibitor 2A (CDKN2A), and CDKN2A homozygous deletion (HD) is a novel CNS WHO grade 4 marker in isocitrate dehydrogenase gene (IDH)-mutant astrocytoma. However, incorporating molecular workup into the "routine diagnostics" of each brain tumor type remains a major challenge, especially in resource-limited settings, including low- and middle-income countries. We herein validated the usefulness of p16 and methylthioadenosine phosphorylase (MTAP) immunohistochemistry (IHC) as potential surrogates for the assessment of CDKN2A status in 20 IDH-mutant astrocytoma cases. Of note, loss or retention of p16 and MTAP could accurately predict CDKN2A HD (p16: 87.5%, MTAP: 88.9%) or non-HD (p16: 100%, MTAP: 100%) with a single marker alone. Importantly, we revealed contributing factors to gray-zone IHC results (p16: 5-20%, MTAP: mosaic), including (1) hemizygous deletion of CDKN2A, (2) degenerative findings, and (3) intratumoral CDKN2A HD heterogeneity, the detailed histologic and molecular assessment of which would be a key to achieving integrated assessment of malignancy in IDH-mutant astrocytoma. We characterized the pitfalls of each method and provided for the first time a practical flowchart of astrocytoma grading, contributing to a normalization of WHO2021-based molecular diagnostics in resource-limited settings.

Oral sildenafil versus bosentan for treatment of persistent pulmonary hypertension of the newborn: a randomized controlled trial.

BACKGROUND: Access to inhaled nitric oxide (iNO) is limited in low resource settings due to non-availability and high cost. There is a need for research on low-cost alternative therapies for management of persistent pulmonary hypertension of the newborn (PPHN). We aimed to compare oral sildenafil and bosentan as monotherapy in the treatment of neonates with PPHN. STUDY DESIGN: In this single-centre open-label randomized controlled trial (RCT), term and late preterm neonates with PPHN, defined as pulmonary arterial systolic pressure (PASP) > 35 mmHg and requiring fraction of inspired oxygen (FiO2) > 0.21, were randomized to receive oral sildenafil and bosentan. The primary outcome was reduction of PASP by 25% within 48 h after start of drug. RESULTS: Thirty-six neonates were analyzed (18 in each group). Initial PASPs were similar in both groups. The median (IQR) time for the primary outcome (PASP to reduce by 25% within 48 h) was 36 (24-48) h and 96 (48-120) h in sildenafil and bosentan groups respectively (p = 0.008). There was also a higher need to add other pulmonary vasodilators in bosentan group as compared to sildenafil group (p = 0.006). CONCLUSION: Sildenafil was associated with quicker reduction of PASP and FiO2 in neonates with PPHN, as compared to bosentan. Large multicentre blinded trials to assess efficacy and safety of bosentan in comparison with other pulmonary vasodilators would help to get a clearer understanding of its role in the management of PPHN, particularly for use in resource-limited settings that lack iNO. CLINICAL TRIAL REGISTRATION: https://ctri.nic.in/Clinicaltrials/rmaindet.php? trialid=63997&EncHid=39716.16132&modid=1&compid=19[CTRI/2022/06/043328].