Retrospective Diagnosis Research Articles

Characterizing Pediatric Familial Adenomatous Polyposis in Patients Undergoing Colectomy in the United States

To characterize a multi-institutional cohort of pediatric patients who underwent colectomy for familial adenomatous polyposis (FAP). In this retrospective cohort study, diagnosis and procedure codes were used to identify patients who underwent colectomy for FAP within the Pediatric Health Information System (PHIS). The inclusion criteria were validated at 3 children's hospitals and applied to PHIS to generate a cohort of patients with FAP between 2 and 21years who had undergone colectomy between 2009 and 2019. Demographics, clinical and surgical characteristics, and endoscopic procedure trends as identified through PHIS are described. Descriptive and comparative statistics were used to analyze data. Within the PHIS, 428 pediatric patients with FAP who underwent colectomy were identified. Median age at colectomy was 14years (range 2-21years); 264 patients (62%) received an ileal pouch anal anastomosis and 13 (3%) underwent ileorectal anastomosis. Specific anastomotic surgical procedure codes were not reported for 151 patients (35%). Endoscopic assessment at the surgical institution occurred in 40% of the cohort before colectomy and in 22% of the cohort following colectomy. In this cohort, colectomy took place at an earlier age than suggested in published guidelines. Ileal pouch anal anastomosis is the predominant procedure for pediatric patients with FAP who underwent colectomy in US pediatric centers. Endoscopic assessment trends before and after surgery suggest that the surgical institution plays a limited role in the care of this population.

Is the Intellectual Functioning Component of AAIDD's 12th Manual Satisficing?

Is the Intellectual Functioning Component of AAIDD's 12th Manual Satisficing?

Microvascular imaging ultrasound (MicroV) and power Doppler vascularization analysis in a pediatric population with early scrotal pain onset.

The power Doppler is a useful tool in the evaluation of pediatric acute scrotal pain. Nonetheless, it may have some inherent limitations in scrotal vascularization analysis, potentially causing unnecessary surgery. The microvascular imaging ultrasound (MicroV) is an innovative Doppler technique able to improve the detection of very low flow. This retrospective study aims to compare both power Doppler and MicroV in the evaluation of a pediatric population with early-stage scrotal pain onset, first in testis vascularization analysis, and second in their diagnostic performances. 69 patients met the following inclusion criteria, age < 18-year-old, a clinical diagnosis of acute scrotal disease, pain onset ≤ 6h, ultrasound examination (including B-mode, power Doppler, and MicroV), 3-months follow-up. For both power Doppler and MicroV, through a defined vascularization scale, it was evaluated the agreement in vascularization detection, and the sensitivity and specificity in US diagnostic abilities. Retrospective diagnoses were of 8 testicular torsion, 15 orchi-epididymitis, and 46 children with other scrotal conditions. Power Doppler provided inconclusive US evaluation in 37.68% of the cases, while MicroV only in the 1.45% (p < 0.0001). Testicular torsion and orchi-epididymitis were identified, respectively, with MicroV in 100% (sensitivity, specificity, PPV, NPV, and accuracy of 100%) and 80% of patients (80% sensitivity, 100% specificity and PPV, 94.73% NPV, 95.65% accuracy); with power Doppler the identification was, respectively, of 87.5% (87.5% sensitivity, 100% specificity and PPV, 98.38% NPV and accuracy) and of 73.3% (73.33% sensitivity, 98.14% specificity, 91.66% PPV, 92.98% NPV, 92.75% accuracy). Our findings indicate that MicroV is a reliable technique in vascularization detection of pediatric testes, being able also to detect vascularization in healthy testicles with no-flow at power Doppler examination. Moreover, MicroV could be a valuable ally in the US diagnostic of children with early-stage scrotal pain onset.

Historical Features Regarding the Neuropathic Outbreaks in Brazilian Troops in the Paraguayan War.

During the Paraguayan War, Brazilian army and navy officers attributed outbreaks of combatant limb weakness with particular features such as tingling to palustrian causes. A dietary basis was not fully suspected at the time, and the popular name beriberi had not been coined. During wartime, there was a shortage in the food supply in addition to poor environmental conditions and diarrheal diseases, and many reports of "palustrian cachexia" were made. There are also reports of the use of native flora to feed troops, as well as alcoholism. There are also accounts of the death of horses with symptoms similar to those of combatants. It was reported that black soldiers were more resistant to "palustrian cachexia." This article presents the disease ecology and clinical manifestations of beriberi at wartime, linked to starvation and consumption of pickled food and native flora. These military explorations and operations in the Paraguayan War happened more than 150 y ago and present some aspects of wilderness medicine in the past.

Incidence of adjacent-segment surgery following stand-alone lateral lumbar interbody fusion.

Adjacent-segment disease (ASD) requiring operative intervention is a relatively common long-term consequence of lumbar fusion surgery. Although the incidence of ASD requiring reoperation is well described for traditional posterior lumbar approaches (2.5%-3.9% per year), it remains poorly characterized for stand-alone lateral lumbar interbody fusion (LLIF). In this study, the authors report their institutional experience with ASD requiring reoperation after LLIF over an extended follow-up period of 4 years. Medical records were reviewed for 276 consecutive patients who underwent stand-alone LLIF by a single surgeon for degenerative spinal disorders. Inclusion criteria (single-stage, stand-alone LLIF without posterior supplementation, with no prior lumbar instrumentation, and a minimum of 4 years of follow-up) were met by 182 patients, who were analyzed for operative ASD incidence (per-year rate), demographics, and Oswestry Disability Index (ODI) score. Operative ASD was strictly defined as new-onset pathology following index surgery at directly adjacent levels to the prior construct. Operative, rather than symptomatic or radiographic, ASD was analyzed to provide a consistent and impactful endpoint while avoiding retrospective diagnosis. The study cohort of 182 patients had an operative ASD rate of 3.3% (n = 6 procedures) over 4 years of follow-up, for an incidence on Kaplan-Meier survival analysis of 0.88% (95% CI 0.67%-1.09%) per year. In comparing patients with operative ASD with those without, there were no significant differences in mean age (53.7 vs 56.2 years), male sex (33.3% vs 44.9%), smoking status (16.7% vs 25.0%), or number of levels fused (mean 1.33 vs 1.46). The operative ASD cohort had a greater mean BMI (37.3 vs 30.2, p < 0.01). Operative ASD patients had lower baseline ODI scores (33.8 vs 48.3, p = 0.02); however, no difference was observed in ODI at 6 weeks (34.0 vs 39.0) or 3 months (16.0 vs 32.8) postoperatively. The incidence of ASD in LLIF for degenerative lumbar etiologies in this cohort was 0.88% (95% CI 0.67%-1.09%) per year. Meanwhile, the reported reoperation rates for ASD in posterior spinal approaches was 2.5% to 3.9% per year, which implies that LLIF may be preferable for well-selected patients.

Development of an immunochromatographic point-of-care test for detection of IgG antibody in serodiagnosis of human trichinellosis

Objective: Trichinellosis is a globally distributed food-borne parasitic disease. Initially, diagnosis is usually made based on clinical signs, symptoms, and history of eating raw or undercooked meat. In the present study, an immunochromatographic test (ICT) kit was developed to diagnose trichinellosis by detecting IgG antibodies in sera of infected humans.Methods: Somatic extract from Trichinella spiralis larvae was used as the antigen for the ICT kit development. Diagnostic efficacy was evaluated using human serum samples from proven trichinellosis patients, healthy persons, and those with other parasitic infections.Results: The diagnostic sensitivity, specificity, positive and negative predictive values and accuracy of the ICT kit were 100.0% (95%; CI 88.8 to 100.0%), 92.5% (95% CI; 86.9 to 96.2%), 73.8% (95% CI; 58.0 to 86.1%), 100.0% (95% CI; 97.3 to 100.0%) and 93.8% (95% CI; 89.2 to 96.9%), respectively.Conclusions: This ICT diagnostic kit can be used as a testing tool for human trichinellosis. This test should permit rapid detection of infection to enable prompt anthelminthic treatment. It can also be used for retrospective diagnoses and field surveys based at laboratories where sophisticated equipment is lacking.

NGS and phenotypic ontology-based approaches increase the diagnostic yield in syndromic retinal diseases

Syndromic retinal diseases (SRDs) are a group of complex inherited systemic disorders, with challenging molecular underpinnings and clinical management. Our main goal is to improve clinical and molecular SRDs diagnosis, by applying a structured phenotypic ontology and next-generation sequencing (NGS)-based pipelines. A prospective and retrospective cohort study was performed on 100 probands with an a priori diagnosis of non-Usher SRDs, using available clinical data, including Human Phenotype Ontology annotation, and further classification into seven clinical categories (ciliopathies, specific syndromes and five others). Retrospective molecular diagnosis was assessed using different molecular and bioinformatic methods depending on availability. Subsequently, uncharacterized probands were prospectively screened using other NGS approaches to extend the number of analyzed genes. After phenotypic classification, ciliopathies were the most common SRD (35%). A global characterization rate of 52% was obtained, with six cases incompletely characterized for a gene that partially explained the phenotype. An improved characterization rate was achieved addressing prospective cases (83%) and well-recognizable syndrome (62%) subgroups. The 27% of the fully characterized cases were reclassified into a different clinical category after identification of the disease-causing gene. Clinical-exome sequencing is the most appropriate first-tier approach for prospective cases, whereas whole-exome sequencing and bioinformatic reanalysis increases the diagnosis of uncharacterized retrospective cases to 45%, mostly those with unspecific symptoms. Our study describes a comprehensive approach to SRDs in daily clinical practice and the importance of thorough clinical assessment and selection of the most appropriate molecular test to be used to solve these complex cases and elucidate novel associations.

Neurosurgical management of vascular compression presenting as visual symptoms secondary to elongated styloid processes (Eagle syndrome)

Background Eagle syndrome (ES) was first described in 1937, to characterize elongation of the styloid process. It is rarely encountered by neurosurgeons but does present the potential for vascular sequelae and neurological complications. Demonstrative cases We discuss three patients with uncommon presentations of neurovascular compromise with uncommon symptomatology, secondary to ES. Their management ranged from retrospective diagnoses following self-limited events, antiplatelet therapy, and endovascular and surgical interventions. Discussion While traumatic fractures, chiropractic manipulation, and history of prior neck surgery have been implicated as the etiologies for ES, congenital cases are common. The styloid process intimately interplays with adjacent neurovascular and nervous structures; its elongation can cause symptoms in 10% of patients. Conclusion Awareness of this potentially dangerous but rare disease – more commonly seen by our otolaryngology colleagues – may help reduce diagnostic delays when an elongated styloid process is the cause, as surgery may be required.

3D МОДЕЛЮВАННЯ ЕКСПЕРИМЕНТАЛЬНОГО РАНОВОГО КАНАЛУ, СПРИЧИНЕНОГО КОЛЮЧЕ-РІЖУЧИМ ЗАСОБОМ З ОДНОБІЧНОЮ ЗАТОЧКОЮ ЛЕЗА

The aim – to carry out 3D modelling of the wound canal formed by a stab-cuttingtool with one-sided sharpening of the blade, using photogrammetry method for furtherinvestigation of its morphological peculiarities and obtaining linear dimensions withhigh accuracy in the space of the graphic editor 3ds Max.Material and methods. Fifteen experimental wound canals were reconstructedby means of an alginate imprinting mass with a rubber-like effect Hydrogum 5(Zhermack, Italy), which hardens quickly, remains elastic after polymerization, allowsto obtain imprints with an extremely smooth surface andmost accurately preserves andreproduces the properties of the immersed in it blade of the knife under study. Astabcutting tool - a knife with one-sided sharpening of the blade, blade length - 9.6 cm,width in the place of the greatest blade thickening - 2.6 cm, butt thickness - 0.24 cmwas used to mark experimental damage. Given dimensions of the stab- cutting toolwere obtained by means of sliding caliper with an error of ± 0.03-0.15 cm. The formedwound canal was divided into fragments with a step of about 3.5 cm. Each fragmentof the wound canal was contrasted with dye (1% alcohol solution of diamond green).These fragments of the wound canal were opened parallel to its length and placed on arotating table, which was located in a light cube to provide sufficient illumination andphotography was performed. A SONY RX 10 II digital camera was used for taking aphotograph. The index number and a fragment of a scale ruler 1.0 cm long were placedon the object for further calibration of the scale and control of the dimensions of theobject under study in computer programs. The photos obtained in JPEG format wereloaded to the computer program Agisoft Photoscan, where 3D textured models of thewound canal fragment were created. The obtained model and texture were exportedin OBJ format. Then the obtained 3D models were moved to the graphic space of theprogram 3ds max to calibrate the scale of the model and in the graphic editor thereconstruction of the wound canal was carried by means of 3D models of its fragments.Results. Measurements of the linear dimentions of damages were carried out at firstby a classical method (by means of a ruler). In addition to, that the depth of the woundcanal, which consists of three fragments, was obtained according to the method ofmeasuring the depth of the wound canal in the body of the corpse by putting togetherits seperate parts in accordance with immersion and permeability of the blade in thevictim's body (skin, subcutaneous muscle tissue, cavity wall and in it itself, the internalorgan and other anatomical formations). Similarly, the width of the wound canal andthe distance between the corners from the side of the butt, which illustrate the thicknessof the blade of the cutting edge and the length of its separate fragments, which in itsturn reproduce the parameters of the blade of an acute traumatic object, were fixed at different levels of immersion.The next stage of our work was to study and obtain the linear dimensions of 3Dmodels’damage by means of a graphic editor 3ds max. In this case, the mentionedcomputer program allowed to obtain the dimensions, described by us,already by anorder with higher accuracy (up to 0.001 cm).The results, obtained by us in the experiment, allow to assert about the high accuracyof measurements, carried out using a computer program for 3D modeling 3ds Max.When combining the obtained linear dimensions of the damage with increased accuracyand the possibility to conduct retrospective diagnosis of the most specific part of thewound canal, formed by the blade belly, the level of accuracy and visualization of thecarried out forensic medical examination is significantly increased.Conclusions. The results, obtained by photogrammetry and 3D modeling of the woundcanal, make it possible to assert the increased accuracy of investigations of individualmorphological characteristics of the lesions and allow to conduct retrospectiveidentification of fragments of the wound canal with the instrument of injury. In additionto that, forensic medical experts receive a modern objective tool for the selection andidentification of the used stab- cutting tool among those provided for examination byjudicial investigation organs. The introduction of the modern methods of 3D modelinginto forensic medical and medical-criminal practice allows to improve the accuracyand visualization of the carrying out examinations and brings them to a new higherlevel.

3D MODELING OF EXPERIMENTAL WOUND CANAL CAUSED BY STABCUTTING TOOL WITH ONE-SIDED SHARPENING OF THE BLADE

The aim – to carry out 3D modelling of the wound canal formed by a stab-cuttingtool with one-sided sharpening of the blade, using photogrammetry method for furtherinvestigation of its morphological peculiarities and obtaining linear dimensions withhigh accuracy in the space of the graphic editor "3ds Max".Material and methods. Fifteen experimental wound canals were reconstructedby means of an alginate imprinting mass with a rubber-like effect "Hydrogum 5"(Zhermack, Italy), which hardens quickly, remains elastic after polymerization, allowsto obtain imprints with an extremely smooth surface andmost accurately preserves andreproduces the properties of the immersed in it blade of the knife under study. Astabcutting tool - a knife with one-sided sharpening of the blade, blade length - 9.6 cm,width in the place of the greatest blade thickening - 2.6 cm, butt thickness - 0.24 cmwas used to mark experimental damage. Given dimensions of the stab- cutting toolwere obtained by means of sliding caliper with an error of ± 0.03-0.15 cm. The formedwound canal was divided into fragments with a step of about 3.5 cm. Each fragmentof the wound canal was contrasted with dye (1% alcohol solution of diamond green).These fragments of the wound canal were opened parallel to its length and placed on arotating table, which was located in a light cube to provide sufficient illumination andphotography was performed. A SONY RX 10 II digital camera was used for taking aphotograph. The index number and a fragment of a scale ruler 1.0 cm long were placedon the object for further calibration of the scale and control of the dimensions of theobject under study in computer programs. The photos obtained in JPEG format wereloaded to the computer program "Agisoft Photoscan", where 3D textured models of thewound canal fragment were created. The obtained model and texture were exportedin OBJ format. Then the obtained 3D models were moved to the graphic space of theprogram "3ds max" to calibrate the scale of the model and in the graphic editor thereconstruction of the wound canal was carried by means of 3D models of its fragments.Results. Measurements of the linear dimentions of damages were carried out at firstby a classical method (by means of a ruler). In addition to, that the depth of the woundcanal, which consists of three fragments, was obtained according to the method ofmeasuring the depth of the wound canal in the body of the corpse by putting togetherits seperate parts in accordance with immersion and permeability of the blade in thevictim's body (skin, subcutaneous muscle tissue, cavity wall and in it itself, the internalorgan and other anatomical formations). Similarly, the width of the wound canal andthe distance between the corners from the side of the butt, which illustrate the thicknessof the blade of the cutting edge and the length of its separate fragments, which in itsturn reproduce the parameters of the blade of an acute traumatic object, were fixed at different levels of immersion.The next stage of our work was to study and obtain the linear dimensions of 3Dmodels’damage by means of a graphic editor "3ds max". In this case, the mentionedcomputer program allowed to obtain the dimensions, described by us,already by anorder with higher accuracy (up to 0.001 cm).The results, obtained by us in the experiment, allow to assert about the high accuracyof measurements, carried out using a computer program for 3D modeling "3ds Max".When combining the obtained linear dimensions of the damage with increased accuracyand the possibility to conduct retrospective diagnosis of the most specific part of thewound canal, formed by the blade belly, the level of accuracy and visualization of thecarried out forensic medical examination is significantly increased.Conclusions. The results, obtained by photogrammetry and 3D modeling of the woundcanal, make it possible to assert the increased accuracy of investigations of individualmorphological characteristics of the lesions and allow to conduct retrospectiveidentification of fragments of the wound canal with the instrument of injury. In additionto that, forensic medical experts receive a modern objective tool for the selection andidentification of the used stab- cutting tool among those provided for examination byjudicial investigation organs. The introduction of the modern methods of 3D modelinginto forensic medical and medical-criminal practice allows to improve the accuracyand visualization of the carrying out examinations and brings them to a new higherlevel.

Optimizing the microscopic agglutination test (MAT) panel for the diagnosis of Leptospirosis in a low resource, hyper-endemic setting with varied microgeographic variation in reactivity.

The microscopic agglutination test (MAT) is the standard serological reference test for the diagnosis of leptospirosis, despite being a technically demanding and laborious procedure. The use of a locally optimised MAT panel is considered essential for proper performance and interpretation of results. This paper describes the procedure of selecting such an optimised panel for Sri Lanka, a country hyper-endemic for leptospirosis. MAT was performed using 24 strains on 1132 serum samples collected from patients presenting with acute undifferentiated fever. Of 24 strains, 15 were selected as the optimised panel, while only 11% of serum samples showed positivity. A geographical variation in predominantly reactive serovars was observed, whereas reactivity was low with the saprophytic strain Patoc. Testing with paired sera yielded a higher sensitivity but provided only a retrospective diagnosis. Serological tests based on ELISA with complementary molecular diagnosis using PCR are a feasible and robust alternative approach to diagnose leptospirosis in countries having a higher burden of the disease.

The Efficacy of Extra-Corporal Photopheresis for Bronchiolitis Obliterans Syndrome after Hematopoietic Cell Transplantation: A Retrospective, Matched, Case-Control Study

Background:Bronchiolitis obliterans syndrome (BOS) is associated with major morbidity and mortality in hematopoietic cell transplant (HCT) recipients. Due to the suboptimal response to conventional therapies, extracorporeal photopheresis (ECP) has been explored as a possible therapeutic option. However, to date, only a few case series, without control groups, examining the effectiveness of ECP for BOS after HCT (Del Fante et al, 2016; Lucid et al, 2011 ), have been published. We carried out this first matched case-control study to assess the impact of ECP therapy for BOS after HCT.Methods:After IRB approval, our institutional database of 304 consecutive AML patients that underwent allogeneic HCT between 2005 and 2015 was reviewed. A retrospective diagnosis of BOS was made in patients who developed a new obstructive pulmonary function test (PFT) with progressive FEV1 decline of ≥ 10% over 3 months without complete resolution on subsequent testing. Patients with BOS diagnosis were classified into case or control groups according to treatment with or without ECP, respectively. ECP was started on a weekly basis with two apheresis sessions a week followed by gradual taper at the discretion of treating physicians. Methoxsalen was administered at a dose of 0.35 mcg per ml of pheresed buffy coat. Propensity score analysis was performed to match cases with controls on a 1:1 ratio. The rate of change in FEV1 (% change from baseline per month) was calculated using linear regression models. Wilcoxon signed-rank test was used to compare paired data at different time intervals.Results:ECP-treated cases consisted of 10 patients (median age 52 years, male 50%), who developed BOS a median of 9 (3-44) months after HCT. ECP was started a median of 9 (range 1-15) months after BOS diagnosis and continued for a median of 50 (range 26-80) sessions. Controls consisted of 24 patients (median age 51 years, male 50%), who developed BOS a median of 10 (range 3-25) months after HCT. There was no significant difference in baseline transplant characteristics between the two groups. Pre-HCT FEV1 was similar between cases and controls (median 92% vs. 99% predicated, p = 0.21). ECP-treated cases, however, had a significantly lower FEV1 at the time of BOS diagnosis (median 48% vs. 68% predicted, p = 0.006) and at six months after non-ECP therapy (median 48% vs. 72% predicted, p = 0.008), consisting of fluticasone/azithromycin/ montelukast (FAM) and/or increased immunosuppression. Propensity score-matched analysis was performed using the covariates of FEV1 nadir and time to FEV1 nadir before ECP initiation or during a matched period for the cases and controls, respectively. Matched controls (n = 10) had similar FEV1 nadir (median 45% vs. 48% predicted, p = 0.76) and time to FEV1 nadir (median 7.5 vs. 9 months, p = 0.81). Within the ECP group, the rate of FEV1 change was significantly more negative before ECP than after ECP (-2.1% / month vs. -0.1% /months; p = 0.004) (Figure 1). Similarly, within the matched control group, the rate of change in FEV1 significantly decreased when periods matched with pre- and post-ECP intervals were compared (median -1.9% / month vs. -0.5% / month; p = 0.03). Across group comparison between ECP and matched controls did not reveal a significant difference in the rate of FEV1 change (p = 0.31). In spite of comparable rates of FEV1 changes between the two groups, and a higher prevalence of non-pulmonary GVHD observed at the time of BOS diagnosis in the ECP group (90% vs. 40%, p = 0.05), patients treated with ECP had a better overall survival in comparison to matched non-ECP controls (estimated median: NR vs. 41 months, p = 0.03) (Figure 2). Two (50%) of 4 deaths in the ECP group and 4 (57%) of 7 deaths in the non-ECP group were attributed to respiratory failure ± superimposed infection.Conclusion:In our retrospective, propensity score-matched analysis, we find that while ECP therapy for HCT patients with BOS did not significantly change FEV1 values in comparison to non-ECP therapies, there was a survival benefit accorded to those treated with ECP. It is plausible that ECP may confer additional benefits that are not reflected in PFTs. This would be best assessed by prospective randomized studies. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Assessment of the burden of malaria and bacteraemia by retrospective molecular diagnosis in febrile illnesses and first-line anti-infectives in Côte d'Ivoire

BackgroundThe aetiologies of fever are poorly understood in sub-Saharan Africa. We aimed to assess the burden of malaria and bacteria in Côte d’Ivoire. MethodsBlood samples from 438 febrile and 346 afebrile people were screened using molecular tools. ResultsPlasmodium falciparum was the most common microorganism associated with fever (46.8% in febrile, 23.4% in afebrile people; p < 0.001). Bacteraemia was detected in 21.7% of febrile people and 12.7% of afebrile people (p = 0.001). Streptococcus pneumoniae was the main cause of bacteraemia (7.1% of febrile and 0.6% of afebrile individuals; p < 0.001). Non-typhoidal Salmonella spp. was detected in 4.5% of febrile people and 1.2% of afebrile individuals (p < 0.001). Salmonella enterica Typhi and S. enterica Paratyphi were only detected in febrile subjects (1.4% and 2.1%), as well as Tropheryma whipplei (0.9%), Streptococcus pyogenes (0.7%), and Plasmodium ovale (4.6%). The prevalence in febrile and afebrile people was similar for Staphylococcus aureus (3.6–4.9%), Rickettsia felis (5.5–6.4%), Mansonella perstans (3.0–3.2%), and Plasmodium malariae (1.6–2.3%). Comorbidities were higher in febrile than in afebrile subjects (10.3% versus 5.5%; p = 0.01); 82% involving P. falciparum. All patients co-infected with P. falciparum and S. pneumoniae were febrile whereas 30% of those infected by P. falciparum alone were not (p = 0.02). Among febrile participants, 30.4% with malaria and 54.7% with bacteraemia had received neither antimalarial nor antibiotic therapy. ConclusionIdentification of etiologies of acute febrile diseases in sub-Saharan Africa proposes keys to successful treatment and prevention of infectious diseases. Vaccination campaigns may decrease the morbidity of mono- and co-infections by preventable microorganisms.

John Goodsir (1814-1867) and his neurological illness.

John Goodsir, conservator and professor of anatomy at the University of Edinburgh, suffered an unidentified illness described by experts after his death as tabes. The features that led to this diagnosis, the understanding of tabes at that time and its relationship in some cases to syphilis, are discussed. It is concluded that the most likely diagnoses are subacute combined degeneration of the cord as a result of malnutrition or tabes dorsalis resulting from earlier syphilis. The presence of 'lightning pains' leans towards the latter diagnosis but evidence for a means of acquisition of syphilis is lacking. The disadvantages of retrospective diagnosis are discussed.

Pathological findings of the retrospective diagnosis of NIFTP (non-invasive follicular thyroid neoplasm with papillary-like nuclear features) in 84 cases from Turkey and systematic review

AimThe terminology of “noninvasive follicular thyroid neoplasm with papillary-like nuclear features” (NIFTP) was introduced in 2016; and estimated to cause significant effects in the clinical management of thyroid nodules. The aim of our study is to review our cases that were previously diagnosed as non-invasive encapsulated follicular variant PTC (NI/E-FVPTC) which are compatible with NIFTP and to correlate their follow-up. MethodAll thyroidectomy cases evaluated in the last 15 years were screened, and possible NIFTP cases were determined among patients with NI/E-FVPTC and they were re-examined microscopically. Revised histopathological criteria were used for the retrospective diagnosis of NIFTP. Histopathological findings were correlated to follow up information. ResultsTotally 2138 cases had been previously diagnosed with PTC; 481 (22.5%) of them were FVPTC. After microscopic reevaluation of potential NIFTP cases, 84 cases (3.9%) received final diagnosis of NIFTP. 78.6% of NIFTP patients were female (F/M: 66/18); mean age was 49.0, tumor diameter was 22.7 mm and follow-up time was 66.4 months. 17.9% of NIFTP cases were multifocal and 13.1% were bilateral. No recurrence, lymph node involvement or distant metastasis was detected in any of the patients who were followed up. The mean age of the patients who had total thyroidectomy and received RAI was significantly higher than those who did not. ConclusionAlthough conservative treatment of NIFTP with lobectomy is recommended, age of the patients has been continuing to be the most important determinant for the clinicians to decide on total thyroidectomy and RAI ablation therapy at our institution.

Characterising Post-mortem Bacterial Translocation Under Clinical Conditions Using 16S rRNA Gene Sequencing in Two Animal Models.

Sudden unexpected death in infancy (SUDI) is the sudden and unexpected death of an apparently healthy infant occurring within the first year of life where the cause is not immediately obvious. It is believed that a proportion of unexplained infant deaths are due to an infection that remains undiagnosed. The interpretation of post-mortem microbiology results is difficult due to the potential false-positives, a source of which is post-mortem bacterial translocation. Post-mortem bacterial translocation is the spread of viable bacteria from highly colonised sites to extra-intestinal tissues. We hypothesise that although post-mortem bacterial translocation occurs, when carcasses are kept under controlled routine clinical conditions it is not extensive and can be defined using 16S rRNA gene sequencing. With this knowledge, implementation of the 16S rRNA gene sequencing technique into routine clinical diagnostics would allow a more reliable retrospective diagnosis of ante-mortem infection. Therefore, the aim of this study was to establish the extent of post-mortem bacterial translocation in two animal models to establish a baseline sequencing signal for the post-mortem process. To do this we used 16S rRNA gene sequencing in two animal models over a 2 week period to investigate (1) the bacterial community succession in regions of high bacterial colonisation, and (2) the bacterial presence in visceral tissues routinely sampled during autopsy for microbiological investigation. We found no evidence for significant and consistent post-mortem bacterial translocation in the mouse model. Although bacteria were detected in tissues in the piglet model, we did not find significant and consistent evidence for post-mortem bacterial translocation from the gastrointestinal tract or nasal cavity. These data do not support the concept of significant post-mortem translocation as part of the normal post-mortem process.

Not all patients with convulsive status epilepticus intubated in pre-hospital settings meet the criteria for refractory status epilepticus

Mechanically ventilated patients admitted to the intensive care unit (ICU) for generalized convulsive status epilepticus (GCSE) are a heterogeneous population. Our objective was to evaluate the number of patients who fulfilled the diagnostic criteria for refractory GCSE and describe their initial management and prognosis. This multicenter retrospective study was conducted in four French ICUs in Pitié-Salpêtrière University Hospital in Paris and in the Hospital of Jossigny. Mechanically ventilated patients admitted to the ICU for GCSE between, January 1, 2014, and, December 31, 2016, were included. Patients with anoxia and traumatic brain injury were excluded. Their pre-hospital and ICU medical records were reviewed. The collected data included pre-hospital clinical status, pre-hospital antiepileptic treatment, reason for mechanical ventilation, duration of general anesthesia, and prognosis in the ICU. A retrospective initial diagnosis based on the findings of the analysis of the clinical records was attributed to each patient. Among the 98 patients included, 88.8% (n=87/98) fulfilled the diagnostic criteria for GCSE; of these cases, 16.1% (n=14/87) were refractory. Eleven percent of the patients did not fulfill the criteria for GCSE at the time of initial management (retrospective diagnosis of single convulsive seizure, repetitive convulsive seizures, or psychogenic non-epileptic seizures). Most patients were intubated for coma (58.9%, n=56/95, missing data: n=3). In the ICU, the median [Q1-Q3] duration of general anesthesia before weaning was 12.3 h (5.0-18.0 h); 7% of the patients had a relapse of status epilepticus, and 2% died in the ICU. Among the cases of confirmed GCSE in the mechanically ventilated patients admitted to the ICU, 16.1% were refractory, with an overall good prognosis. A significant proportion of patients did not fulfill the diagnostic criteria for refractory GCSE.

Recent Advances in the Evaluation of Serological Assays for the Diagnosis of SARS-CoV-2 Infection and COVID-19.

Introduction: Few data on the diagnostic performance of serological tests for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are currently available. We evaluated sensitivity and specificity of five different widely used commercial serological assays for the detection of SARS-CoV-2–specific IgG, IgM, and IgA antibodies using reverse transcriptase-PCR assay in nasopharyngeal swab as reference standard test.Methods: A total of 337 plasma samples collected in the period April–June 2020 from SARS-CoV-2 RT-PCR positive (n = 207) and negative (n = 130) subjects were investigated by one point-of-care lateral flow immunochromatographic assay (LFIA IgG and IgM, Technogenetics) and four fully automated assays: two chemiluminescence immunoassays (CLIA-iFlash IgG and IgM, Shenzhen YHLO Biotech and CLIA-LIAISON® XL IgG, DiaSorin), one electrochemiluminescence immunoassay (ECLIA-Elecsys® total predominant IgG, Roche), and one enzyme-linked immunosorbent assay (ELISA IgA, Euroimmune).Results: The overall sensitivity of all IgG serological assays was >80% and the specificity was >97%. The sensitivity of IgG assays was lower within 2 weeks from the onset of symptoms ranging from 70.8 to 80%. The LFIA and CLIA-iFlash IgM showed an overall low sensitivity of 47.6 and 54.6%, while the specificity was 98.5 and 96.2%, respectively. The ELISA IgA yielded a sensitivity of 84.3% and specificity of 81.7%. However, the ELISA IgA result was indeterminate in 11.7% of cases.Conclusions: IgG serological assays seem to be a reliable tool for the retrospective diagnosis of SARS-CoV-2 infection. IgM assays seem to have a low sensitivity and IgA assay is limited by a substantial rate of indeterminate results.

Genetic Evaluation of the Parents Following Demise of the Index Case: Report of a Family with Fucosidosis.

It is common in obstetric practice to encounter couples who seek prenatal genetic counseling and testing in view of history of known or suspected genetic disorders in the previous offspring or in other family members. Recent advances in genetic testing techniques, especially the availability of the next-generation sequencing (NGS) technology, have greatly facilitated genetic evaluation of the proband and/or the consultand couple and enabled provision of accurate genetic counseling and prenatal genetic testing in such clinical scenarios. However, even in this era of NGS, comprehensive clinical history taking and detailed phenotype characterization through clinical examination and thorough perusal of available medical records, are very important and essential for accurate diagnosis, as reiterated by this report of a 30-year-old third gravida, who was referred for prenatal genetic counseling and testing, in view of history of death of the first offspring due to a suspected neurogenetic disorder. Retrospective clinical diagnosis for the deceased index child with the help of available medical records and reports, followed by relevant NGS-based clinical exome sequencing of the couple, helped to arrive at a definitive diagnosis of fucosidosis, based on which accurate prenatal genetic testing could be done.

Laboratory-Based Resources for COVID-19 Diagnostics: Traditional Tools and Novel Technologies. A Perspective of Personalized Medicine.

The coronavirus infection 2019 (COVID-19) pandemic, caused by the highly contagious SARS-CoV-2 virus, has provoked a global healthcare and economic crisis. The control over the spread of the disease requires an efficient and scalable laboratory-based strategy for testing the population based on multiple platforms to provide rapid and accurate diagnosis. With the onset of the pandemic, the reverse transcription polymerase chain reaction (RT-PCR) method has become a standard diagnostic tool, which has received wide clinical use. In large-scale and repeated examinations, these tests can identify infected patients with COVID-19, with their accuracy, however, dependent on many factors, while the entire process takes up to 6–8 h. Here we also describe a number of serological systems for detecting antibodies against SARS-CoV-2. These are used to assess the level of population immunity in various categories of people, as well as for retrospective diagnosis of asymptomatic and mild COVID-19 in patients. However, the widespread use of traditional diagnostic tools in the context of the rapid spread of COVID-19 is hampered by a number of limitations. Therefore, the sharp increase in the number of patients with COVID-19 necessitates creation of new rapid, inexpensive, sensitive, and specific tests. In this regard, we focus on new laboratory technologies such as loop mediated isothermal amplification (LAMP) and lateral flow immunoassay (LFIA), which have proven to work well in the COVID-19 diagnostics and can become a worthy alternative to traditional laboratory-based diagnostics resources. To cope with the COVID-19 pandemic, the healthcare system requires a combination of various types of laboratory diagnostic testing techniques, whodse sensitivity and specificity increases with the progress in the SARS-CoV-2 research. The testing strategy should be designed in such a way to provide, depending on the timing of examination and the severity of the infection in patients, large-scale and repeated examinations based on the principle: screening–monitoring–control. The search and development of new methods for rapid diagnostics of COVID-19 in laboratory, based on new analytical platforms, is still a highly important and urgent healthcare issue. In the final part of the review, special emphasis is made on the relevance of the concept of personalized medicine to combat the COVID-19 pandemic in the light of the recent studies carried out to identify the causes of variation in individual susceptibility to SARS-CoV-2 and increase the efficiency and cost-effectiveness of treatment.