Practice of percutaneous needle autopsy; a descriptive study reporting experiences from Uganda

BACKGROUND: Percutaneous needle autopsy can overcome a number of barriers that limit the use of complete autopsies. We performed blind-and ultrasound guided needle autopsies in HIV-infected adults in Uganda. In this study we describe in detail the methods we used, the ability of both procedures to obtain sufficient tissue for further examination and the learning curve of the operators over time. METHODS: If written informed consent was granted from the next of kin, we first performed a blind needle autopsy, puncturing brain, heart, lungs, liver, spleen and kidneys using predefined surface marking points. We then performed an ultrasound guided needle autopsy puncturing heart, liver, spleen and kidneys. The number of attempts, expected success and duration of the procedure were noted. A pathologist read the slides and indicated if the target tissue was present and of sufficient quality for pathological review. We report the predicted and true success rates, compare the yield of blind to ultrasound guided needle biopsies and evaluate the failure rate over time. RESULTS: Two operators performed 96 blind needle autopsies and 95 ultrasound guided needle autopsies. For blind needle biopsies true success rates varied from 56-99% and predicted success rates from 89-99%. For ultrasound guided needle biopsies true success rates varied from 72-100% and predicted success rates from 84-98%. Ultrasound guidance led to a significantly higher success rate in heart and left kidney. A learning curve was observed over time with decreasing failure rates with increasing experience and a shorter duration of the needle autopsy. CONCLUSION: Needle autopsy can successfully obtain tissue for further pathological review in the vast majority of cases, with a decrease in failure rate with increasing experience of the operator. The benefit of ultrasound guidance will depend on the population, the disease and organ of interest and the local circumstances. Our results justify further evaluation of needle autopsies as a method to establish a cause of death

The clinical value of minimal invasive autopsy in COVID-19 patients

Background Minimally invasive autopsy (MIA) is a validated and safe method to establish the cause of death (COD), mainly in low-resource settings. However, the additional clinical value of MIA in Coronavirus disease (COVID-19) patients in a high-resource setting is unknown. The objective was to assess if and how MIA changed clinical COD and contributing diagnoses in deceased COVID-19 patients. Methods and findings A prospective observational cohort from April to May 2020 in a 981-bed teaching hospital in the epicenter of the COVID-19 pandemic in Belgium was established. Patients who died with either PCR-confirmed or radiologically confirmed COVID-19 infection were consecutively included. MIA consisted of whole-body CT and CT-guided Tru-Cut (R) biopsies. Diagnostic modalities were clinical chart review, radiology, microbiology, and histopathology which were assessed by two independent experts per modality. MIA COD and contributing diagnoses were established during a multi-disciplinary meeting. Clinical COD (CCOD) and contributing diagnosis were abstracted from the discharge letter. The main outcomes were alterations in CCOD and contributing diagnoses after MIA, and the contribution of each diagnostic modality. We included 18 patients, of which 7 after intensive care unit hospitalization. MIA led to an alteration in 15/18 (83%) patients. The CCOD was altered in 5/18 (28%) patients. MIA found a new COD (1/5), a more specific COD (1/5), a less certain COD (1/5), or a contributing diagnosis to be the COD (2/5). Contributing diagnoses were altered in 14/18 (78%) patients: 9 new diagnoses, 5 diagnoses dismissed, 3 made more specific, and 2 made less certain. Overall, histopathology contributed in 14/15 (93%) patients with alterations, radiology and microbiology each in 6/15 (40%), and clinical review in 3/15 (20%). Histopathology was deemed the most important modality in 10 patients, radiology in two patients, and microbiology in one patient. Conclusion MIA, especially histological examination, can add valuable new clinical information regarding the cause of death in COVID-19 patients, even in a high-resource setting with wide access to premortem diagnostic modalities. MIA may provide important clinical insights and should be applied in the current ongoing pandemic

An Autopsy Study Describing Causes of Death and Comparing Clinico-Pathological Findings among Hospitalized Patients in Kampala, Uganda

Background: Information on causes of death in HIV-infected patients in Sub-Saharan Africa is mainly derived from observational cohort and verbal autopsy studies. Autopsy is the gold standard to ascertain cause of death. We conducted an autopsy study to describe and compare the clinical and autopsy causes of death and contributory findings in hospitalized HIV-infected and HIV-uninfected patients in Uganda. Methods: Between May and September 2009 a complete autopsy was performed on patients that died on a combined infectious diseases gastroenterology ward in Mulago Hospital in Kampala, Uganda. Autopsy cause of death and contributing findings were based on the macro- and microscopic post-mortem findings combined with clinical information. Clinical diagnoses were reported by the ward doctor and classified as confirmed, highly suspected, considered or not considered, based on information derived from the medical chart. Results are reported according to HIV serostatus. Results: Fifty-three complete autopsies were performed in 66 % HIV-positive, 21 % HIV-negative and 13 % patients with an unknown HIV serological status. Infectious diseases caused death in 83 % of HIV-positive patients, with disseminated TB as the main diagnosis causing 37 % of deaths. The spectrum of illness and causes of death were substantially different betwee

Flecainide Is Associated With a Lower Incidence of Arrhythmic Events in a Large Cohort of Patients With Catecholaminergic Polymorphic Ventricular Tachycardia

BACKGROUND: In severely affected patients with catecholaminergic polymorphic ventricular tachycardia, beta-blockers are often insufficiently protective. The purpose of this study was to evaluate whether flecainide is associated with a lower incidence of arrhythmic events (AEs) when added to beta-blockers in a large cohort of patients with catecholaminergic polymorphic ventricular tachycardia. METHODS: From 2 international registries, this multicenter case cross-over study included patients with a clinical or genetic diagnosis of catecholaminergic polymorphic ventricular tachycardia in whom flecainide was added to beta-blocker therapy. The study period was defined as the period in which background therapy (ie, beta-blocker type [beta1-selective or nonselective]), left cardiac sympathetic denervation, and implantable cardioverter defibrillator treatment status, remained unchanged within individual patients and was divided into pre-flecainide and on-flecainide periods. The primary end point was AEs, defined as sudden cardiac death, sudden cardiac arrest, appropriate implantable cardioverter defibrillator shock, and arrhythmic syncope. The association of flecainide with AE rates was assessed using a generalized linear mixed model assuming negative binomial distribution and random effects for patients. RESULTS: A total of 247 patients (123 [50%] females; median age at start of flecainide, 18 years [interquartile range, 14-29]; median flecainide dose, 2.2 mg/kg per day [interquartile range, 1.7-3.1]) were included. At baseline, all patients used a beta-blocker, 70 (28%) had an implantable cardioverter defibrillator, and 21 (9%) had a left cardiac sympathetic denervation. During a median pre-flecainide follow-up of 2.1 years (interquartile range, 0.4-7.2), 41 patients (17%) experienced 58 AEs (annual event rate, 5.6%). During a median on-flecainide follow-up of 2.9 years (interquartile range, 1.0-6.0), 23 patients (9%) experienced 38 AEs (annual event rate, 4.0%). There were significantly fewer AEs after initiation of flecainide (incidence rate ratio, 0.55 [95% CI, 0.38-0.83]; P=0.007). Among patients who were symptomatic before diagnosis or during the pre-flecainide period (n=167), flecainide was associated with significantly fewer AEs (incidence rate ratio, 0.49 [95% CI, 0.31-0.77]; P=0.002). Among patients with ≥1 AE on beta-blocker therapy (n=41), adding flecainide was also associated with significantly fewer AEs (incidence rate ratio, 0.25 [95% CI, 0.14-0.45]; P&lt;0.001). CONCLUSIONS: For patients with catecholaminergic polymorphic ventricular tachycardia, adding flecainide to beta-blocker therapy was associated with a lower incidence of AEs in the overall cohort, in symptomatic patients, and particularly in patients with breakthrough AEs while on beta-blocker therapy.</p

A pathway proteomic profile of ischemic stroke survivors reveals innate immune dysfunction in association with mild symptoms of depression: a pilot study

Depression after stroke is a common occurrence, raising questions as to whether depression could be a long-term biological and immunological sequela of stroke. Early explanations for post-stroke depression (PSD) focused on the neuropsychological/psychosocial effects of stroke on mobility and quality of life. However, recent investigations have revealed imbalances of inflammatory cytokine levels in association with PSD, though to date, there is only one published proteomic pathway analysis testing this hypothesis. Thus, we examined the serum proteome of stroke patients (n = 44, mean age = 63.62 years) and correlated these with the Montgomery–Åsberg Depression Rating Scale (MADRS) scores at 3 months post-stroke. Overall, the patients presented with mild depression symptoms on the MADRS, M = 6.40 (SD = 7.42). A discovery approach utilizing label-free relative quantification was employed utilizing an LC-ESI–MS/MS coupled to a LTQ-Orbitrap Elite (Thermo-Scientific). Identified peptides were analyzed using the gene set enrichment approach on several different genomic databases that all indicated significant downregulation of the complement and coagulation systems with increasing MADRS scores. Complement and coagulation systems are traditionally thought to play a key role in the innate immune system and are established precursors to the adaptive immune system through pro-inflammatory cytokine signaling. Both systems are known to be globally affected after ischemic or hemorrhagic stroke. Thus, our results suggest that lowered complement expression in the periphery in conjunction with depressive symptoms post-stroke may be a biomarker for incomplete recovery of brain metabolic needs, homeostasis, and inflammation following ischemic stroke damage. Further proteomic investigations are now required to construct the temporal profile, leading from acute lesion damage to manifestation of depressive symptoms. Overall, the findings provide support for the involvement of inflammatory and immune mechanisms in PSD symptoms and further demonstrate the value and feasibility of the proteomic approach in stroke research

Temporal trends in death causes in adults attending an urban HIV clinic in Uganda : a restrospective chart review

OBJECTIVE: To study temporal trends of mortality in HIV-infected adults who attended an HIV clinic in Kampala, Uganda, between 2002 and 2012. DESIGN: Descriptive retrospective study. METHODS: Two doctors independently reviewed the clinic database that contained information derived from the clinic files and assigned one or more causes of death to each patient >18 years of age with a known date of death. Four cause-of-death categories were defined: ‘communicable conditions and AIDS-defining malignancies’, ‘chronic non-communicable conditions’, ‘other non-communicable conditions’ and ‘unknown’. Trends in cause-of-death categories over time were evaluated using multinomial logistic regression with year of death as an independent continuous variable. RESULTS: 1028 deaths were included; 38% of these individuals were on antiretroviral therapy (ART). The estimated mortality rate dropped from 21.86 deaths/100 person years of follow-up (PYFU) in 2002 to 1.75/100 PYFU in 2012. There was a significant change in causes of death over time (p<0.01). Between 2002 and 2012, the proportion of deaths due to ‘communicable conditions and AIDS-defining malignancies’ decreased from 84% (95% CI 74% to 90%) to 64% (95% CI 53% to 74%) and the proportion of deaths due to ‘chronic non-communicable conditions’, ‘other non-communicable conditions’ and a combination of ‘communicable and non-communicable conditions’ increased. Tuberculosis (TB) was the main cause of death (34%). Death from TB decreased over time, from 43% (95% CI 32% to 53%) in 2002 to a steady proportion of approximately 25% from 2006 onwards (p<0.01). CONCLUSIONS: Mortality rate decreased over time. The proportion of deaths from communicable conditions and AIDS-defining malignancies decreased and from non-communicable diseases, both chronic and non-chronic, increased. Nevertheless, communicable conditions and AIDS-defining malignancies continued to cause the majority of deaths, with TB as the main cause. Ongoing monitoring of cause of death is warranted and strategies to decrease mortality from TB and other common opportunistic infections are essential

Validation of Walking Speed Estimation from Trunk Mounted Accelerometers for a Range of Walking Speeds

Walking speed is a strong indicator of the health status of older people and patients. Using algorithms, the walking speed can be estimated from wearable accelerometers, which enables minimally obtrusive (longitudinal) monitoring. We evaluated the performance of two algorithms, the inverted pendulum (IP) algorithm, and a novel adaptation correcting for lateral step movement, which aimed to improve accuracy during slow walking. To evaluate robustness, we gathered data from different groups (healthy adults, elderly, and elderly patients) of volunteers (n = 159) walking under various conditions (over ground, treadmill, using walking aids) at a broad range of speeds (0.11–1.93 m/s). Both of the algorithms showed good agreement with the reference values and similar root-mean-square errors (RMSEs) for walking speeds ≥0.5 m/s, which ranged from 0.09–0.16 m/s for the different positions, in line with the results from others. However, for slower walking, RMSEs were significantly better for the new method (0.06–0.09 m/s versus 0.15–0.19 m/s). Pearson correlation improved for speeds &lt;0.5 m/s (from 0.67–0.72 to 0.73–0.82) as well as higher speeds (0.87–0.97 to 0.90–0.98) with the new method. Overall, we found that IP(-based) walking speed estimation proved to be applicable for a variety of wearing positions, conditions and speeds, indicating its potential value for health assessment applications