Index Case Research Articles

Disease intervention specialist-delivered interventions and other partner services for HIV and sexually transmitted infections: A systematic review.

Disease intervention specialists (DIS) are critical for delivering partner services programs that provide partner notification, counseling, referral, and other services for HIV, sexually transmitted infections (STIs), and other infections. This systematic review of partner services and other DIS-delivered interventions for HIV and STIs was conducted to summarize the effectiveness of these programs and identify evidence gaps. A systematic literature review was conducted with a narrative synthesis. Articles were located using keyword searches in MEDLINE, Web of Science, CINAHL, and ProQuest through December 2022 and analyzed in 2023-2024. Included studies addressed an intervention of partner services or other DIS-delivered services for HIV or STIs; a United States setting; primary data collection; and an external comparison group or pre-post design. 1,915 unique records were screened for eligibility, with 30 studies included. Overall, DIS-delivered interventions improved clinical outcomes among index patients and population outcomes. Many studies focused on program process measures rather than population-level epidemiologic outcomes. All but one studies were scored as having low or medium strength of evidence. The evidence could be strengthened by establishing a streamlined set of core metrics, assessing impact using rigorous causal inference methodologies, linking program and clinical data systems, and supplementing impact evaluations with evidence on implementation strategies.

Effectiveness of preventive treatment among different age groups and Mycobacterium tuberculosis infection status: a systematic review and individual-participant data meta-analysis of contact tracing studies.

Tuberculosis is a preventable disease. However, there is debate regarding which individuals would benefit most from tuberculosis preventive treatment and whether these benefits vary in settings with a high burden and low burden of tuberculosis. We aimed to compare the effectiveness of tuberculosis preventive treatment in exposed individuals of differing ages and Mycobacterium tuberculosis infection status while considering tuberculosis burden of the settings. In this systematic review and individual-participant meta-analysis, we investigated the development of incident tuberculosis in people closely exposed to individuals with tuberculosis. We searched for studies published between Jan 1, 1998, and April 6, 2018, in MEDLINE, Web of Science, BIOSIS, and Embase. We restricted our search to cohort studies; case-control studies and outbreak reports were excluded. Two reviewers evaluated titles, abstracts, and full text articles for eligibility. At each stage, two reviewers discussed discrepancies and re-evaluated articles until a consensus was reached. Individual-participant data and a pre-specified list of variables, including characteristics of the exposed contact, the index patient, and environmental characteristics, were requested from authors of all eligible studies; contacts exposed to a drug-resistant tuberculosis index patient were excluded. The primary study outcome was incident tuberculosis. We estimated adjusted hazard ratios (aHRs) for incident tuberculosis with mixed-effects Cox regression models with a study-level random effect. We estimated the number-needed-to-treat (NNT) to prevent one person developing tuberculosis. Propensity score matching procedures were used in all analyses. This study is registered with PROSPERO (CRD42018087022). After screening 25 358 records for eligibility, 439 644 participants from 32 cohort studies were included in the individual-participant data meta-analysis. Participants were followed for 1 396 413 person-years (median of 2·7 years [IQR 1·3-4.4]), during which 2496 people were diagnosed with incident tuberculosis. Overall, effectiveness of preventive treatment was 49% (aHR 0·51 [95% CI 0·44-0·60]). Participants with a positive tuberculin-skin-test (TST) or IFNγ release assay (IGRA) result at baseline benefitted from greater protection, regardless of age (0·09 [0·05-0·17] in children younger than 5 years, 0·20 [0·15-0·28] in individuals aged 5-17 years, and 0·17 [0·13-0·22] in adults aged 18 years and older). The effectiveness of preventive treatment was greater in high-burden (0·31 [0·23-0·40]) versus low-burden (0·58 [0·47-0·72]) settings. The NNT ranged from 9 to 34 depending on age among participants with a positive TST or IGRA in both high-burden and low-burden settings; among all contacts (regardless of TST or IGRA test result), the NNT ranged from 29 to 43 in high-burden settings and 213 to 455 in low-burden settings. Our findings suggest that a risk-targeted strategy prioritising contacts with evidence of M tuberculosis infection might be indicated in low-burden settings, and a broad approach including all contacts should be considered in high-burden settings. Preventive treatment was similarly effective among contacts of all ages. None.

Conditions Associated With Hypertriglyceridemia in Adult Patients in a Tertiary Care Center in Basrah, Iraq.

Background Hypertriglyceridemia (HTG) is one of the major modifiable risk factors for the development of several metabolic diseases. Determining the factors associated with HTG is an important step for increasing awareness of the problem and proper planning of health programs for HTG prevention. This study aimed to determine the conditions associated with HTG in adult patients in Basrah, Iraq. Methodology This retrospective study was conducted at Faiha Specialized Diabetes Endocrine and Metabolism Center (FDEMC) in Basra, southern Iraq, in January 2024. The data were retrieved from the center database of 37,133 subjects registered from 2008 to 2023 (16,284, 43.8% males and 20,849, 56.2% females) who attended the FDEMC in Basra due to different reasons. Results The most common causes of HTG were type 2 diabetes mellitus (T2DM) (29,799, 80%), obesity (19,914, 53.63%), and smoking (7,309, 12.68%). The age group of 18-45 years displayed higher triglyceride (TG) levels (281.1 ± 210.1 mg/dL) than other age groups. Furthermore, male patients had higher TG levels than females (288.0 ± 196.3 mg/dL vs. 268.9 ± 165.9 mg/dL). Regarding body mass index, overweight and obese patients had higher mean TG levels (284.4 ± 182.1 mg/dL and 281.7 ± 184.6 mg/dL, respectively). Current and ex-smokers had higher TG levels (305.1 ± 212.2 mg/dL and 283.4 ± 161.3 mg/dL, respectively) than non-smokers (272.5 ± 175.4 mg/dL). Moderate HTG was the most common category encountered in 24,137 patients (65%), followed by mild HTG (12,705, 34.2%). Very few patients had severe (264, 7%) or very severe HTG (27, 0.07%). Male patients had more frequent severe and very severe HTG than females. Conclusions The most common conditions associated with HTG were T2DM, obesity, and smoking. Smoker males were prone to severe and very severe HTG.

GPS and GIS Based Soil Mapping of Rajkot City

Abstract Traditional (Classical) soil mapping is inefficient in illustrating continuous changes in soil types or forms. Before designing and constructing any construction, geotechnical engineers should be aware of changes in the index qualities of the soil. Sand, Gravel, Silt and Clay, Plastic Limit, and other soil index values may vary from location to location. This work aims to develop a system for mapping important soil index features using GPS and GIS in conjunction with previously published soil exploration data. This database will allow geotechnical engineers to run more searches on various combinations of soil properties. During this study, data from 112 boreholes in Rajkot was compiled into soil investigation reports by various geotechnical specialists. All 112 boreholes are included in a soil database. GPS has been used to figure out each location’s longitude, latitude & altitude for georeferencing. The ordinary kriging geospatial interpolation method was used for thematic map preparation. In this 10% of boreholes, data has been used for validation. Map accuracy is measured using the Mean Average Error (MAE) and the Root Mean Squared Error (RMSE). Where the difference in values were not more than 10% in all 12 cases. The value is only crossed in the plastic index case, where it is more than 10% in the 1-2-meter depth case.

Intrafamilial Disease Heterogeneity in Primary Hyperoxaluria Type 1

Primary hyperoxaluria type 1 (PH1) is known for its variable clinical course, even within families. However, the extent of this heterogeneity has not been well-studied. We aimed to analyze intrafamilial clinical heterogeneity and disease course among siblings in a large cohort of familial PH1 cases. A retrospective registry study was performed using data from OxalEurope. All PH1 families with 2 or more affected siblings were included. A 6-point PH1 clinical outcome scoring system was developed to grade heterogeneity within a family. Intrafamilial clinical heterogeneity was defined as a score≥2. Kaplan-Meier analyses were used to analyze differences in kidney survival between index cases and siblings. We included 88 families, encompassing 193 patients with PH1. The median interquartile range (IQR) follow-up time was 7.8 (1.9-17) years. Intrafamilial clinical heterogeneity, as defined by our score, was found in 38 (43%) PH1 families. In 54% of the families, affected siblings had a better outcome than the index case. Clinically asymptomatic siblings at the time of their diagnosis had a significantly more favorable clinical outcome based on the authors' scoring system than siblings with clinical signs and index cases (P< 0.001). Kaplan-Meier analyses revealed that index cases reached kidney failure at an earlier age and earlier in follow-up compared to siblings (P< 0.001). Intrafamilial clinical heterogeneity was found in a substantial number of familial PH1 cases. Compared to index cases, siblings had significantly better clinical outcomes and kidney survival; thereby supporting the policy of family screening to diagnose affected siblings early to improve their prognosis.

A family with neuronal intranuclear inclusion disease with focal segmental glomerulosclerosis.

Neuronal intranuclear inclusion disease (NIID) is a rare neurodegenerative disease caused by the expansion of GGC repeats in the 5'-untranslated region (5'-UTR) of NOTCH2NLC. Although increasing evidence suggests that NIID affects various organs, its association with renal involvement remains unclear. We studied the genetic background of a family with NIID, in which four of five members presented with proteinuria as the initial manifestation. The renal pathology of three patients was diagnosed as focal segmental glomerulosclerosis (FSGS) at a previous hospital. These patients also presented with tremors, retinal degeneration, and episodic neurological events. Finally, one patient exhibited reversible bilateral thalamic high-intensity signal changes on diffusion-weighted imaging during episodic neurological events. Exome sequencing (ES) and nanopore long-read whole-genome sequencing (LR-WGS) were performed on the index case, followed by nanopore target sequencing using Cas9-mediated PCR-free enrichment and methylation analysis. ES revealed no candidate variants; however, nanopore LR-WGS in the index case revealed expansion of short tandem repeats (STR) in NOTCH2NLC. Subsequent nanopore target sequencing using Cas9-mediated PCR-free enrichment showed STR expansion of NOTCH2NLC in an affected sibling and asymptomatic father. Methylation analysis using nanopore data revealed hypermethylation of the expanded allele in the asymptomatic father and partial hypermethylation in a mildly symptomatic sibling, whereas the expanded allele was hypomethylated in the index case. This investigation expands the clinical spectrum of NIID, suggesting that STR expansion of NOTCH2NLC is a cause of renal diseases, including FSGS.

Two cases demonstrate an association between Tropheryma whipplei and pulmonary marginal zone lymphoma

BackgroundMarginal zone lymphomas of mucosa-associated lymphatic tissues (MZL of MALT) are a group of indolent B-cell neoplasms, which are thought to arise from chronic antigenic stimulation of B-cells either due to underlying chronic infection or autoimmune disease. Little is known about potential causative pathogens in pulmonary MZL (PMZL), although some data suggests a potential role of Achromobacter (A.) xylosoxidans.MethodsAn index case of chronic pulmonary colonisation with Tropheryma (T.) whipplei and subsequent development of PMZL was identified by T. whipplei specific PCR and metagenomic next genome sequencing (mNGS). This case prompted a retrospectively conducted analysis of T. whipplei-specific PCRs in lung tissue from PMZL patients (n = 22), other pulmonary lymphomas, and normal controls. Positive results were confirmed by mNGS. A systematic search for T. whipplei and A. xylosoxidans in our in-house mNGS dataset comprising autopsy lungs, lung biopsies and lung resection specimens (n = 181) was subsequently performed.ResultsA 69-year-old patient presented with weight loss and persistent pulmonary consolidation. Subsequent mNGS analysis detected T. whipplei in the resected lung specimen. An antibiotic regimen eventually eliminated the bacterium. However, the consolidation persisted, and the diagnosis of PMZL was made in a second lung resection specimen. A second case of T. whipplei-associated PMZL was subsequently detected in the retrospectively analysed PMZL cohort. Both cases showed comparatively few mutations and no mutations in genes encoding for NF-κB pathway components, suggesting that T. whipplei infection may substitute for mutations in these PMZL. None of the samples in our in-house dataset tested positive for T. whipplei. In contrast, A. xylosoxidans was frequently found in both autopsy lungs and lung biopsy / resection specimens that were not affected by PMZL (> 50%).ConclusionsOur data suggests that T. whipplei colonisation of lungs may trigger PMZL as a potential driver. Systematic analyses with larger cohorts should be conducted to further support this hypothesis. The frequent detection of A. xylosoxidans in lung tissue suggests that it is a common component of the pulmonary microbiome and therefore less likely to trigger lymphomas.

Ability to Recontact Sex Partners and Partner Treatment Success Among Young Heterosexual Black Men With Chlamydia

PurposePatient-delivered partner therapy (PDPT) allows index patients who test positive for Chlamydia trachomatis (Ct) to provide treatment to partners directly. PDPT is contingent upon an index being able to contact their partner. The aims of this study were to assess factors related to being able to contact a partner and being able to successfully deliver their treatment. MethodsParticipants were Black men who have sex with women aged 15–26 enrolled in a community Ct screening/treatment program in New Orleans, LA who tested positive for Ct and completed a computer-assisted survey. Factors associated with the index's ability to contact their recent sex partner(s) and to successfully deliver PDPT to his partner(s) were compared by characteristics of the relationship. ResultsOf 104 young men who tested positive for Ct, the median age was 20.3 years and information was reported on 184 female partners, of whom 143 (77.7%) were deemed contactable by the index. Only the index wanting to have sex with the partner again was significantly associated with their ability to contact the partner (odds ratio [OR] 5.38, 95% confidence interval [CI] 2.18, 13.23). Only 72/184 (39.1%) partners received PDPT. The index being interested in sex with partner again (OR 2.54, 95% CI 1.23–5.27) was associated with greater odds of successful PDPT delivery whereas if index believed their partner had other partners, successful PDPT was less likely (OR 0.51, 95% CI 0.26–0.99). There was low agreement between an index's ability to contact their partner and the delivery of PDPT (kappa = 0.04 [−0.062, 0.143). DiscussionAsking patients if they can recontact prior sexual parters may be insufficient to ensure that their partners receive PDPT.

Effects of the Beijing genotype on latent tuberculosis infection, TB disease risk, and clustering of TB cases

BackgroundThe Beijing genotype of Mycobacterium tuberculosis (Mtb) has sparked debate regarding its virulence and transmissibility. This study contributes to this discussion by assessing its effect on the risk of latent tuberculosis infection (LTBI), active tuberculosis (TB) disease among contacts, and clustering of known TB cases. MethodsWe conducted a retrospective cohort study using the records of 4457 culture-confirmed TB patients and their contacts (20,448) reported to the Florida Department of Health between 2009 and 2023. Univariate and multivariate analyses were used to evaluate the effect of the Beijing strain on LTBI, active TB risk among contacts, and case clustering. ResultsOur study revealed no significant difference in transmissibility between the Beijing and non-Beijing genotypes among contacts. LTBI prevalence was 19.9%, slightly higher in non-Beijing than Beijing genotypes (20.2% vs. 15.5%, p < 0.001). The prevalence of active TB was 1.8%, with no significant difference between the Beijing and non-Beijing genotypes (1.4% vs. 1.8%, p = 0.296). Increased LTBI risk was associated with older age, male sex, Hispanic ethnicity, multidrug-resistant TB exposure, household exposure, and a longer exposure duration. Active TB risk was higher for males, HIV-positive individuals, and contacts with more prolonged exposure to index cases. The Beijing genotype was associated with increased TB case clustering (aOR = 1.98, 95%CI: 1.53, 2.55, p < 0.001) as compared to the non-Beijing genotypes. US birthplace (aOR = 2.75, 95%CI: 2.37, 3.19, p < 0.001), pulmonary disease (aOR = 1.27, 95%CI: 1.04, 1.56, p < 0.020), cavitary TB (aOR = 1.25, 95% CI: 1.08, 1.44, p < 0.003), previous year alcohol use (aOR = 1.68, 95%CI: 1.38, 2.04, p < 0.001), and recreational drug use (aOR = 1.32, 95%CI: 1.04, 1.67, p < 0.024) were also associated with an increased risk of TB case clustering. ConclusionWhile the Beijing genotype did not increase the risk of LTBI or active TB among contacts, it showed a higher tendency for case clustering. Hence, interventions should prioritize populations where this genotype is prevalent.

Outcomes of robot-assisted laparoscopic pyeloplasty among pediatric patients with complex renal anatomy: A retrospective comparative study

Robot-assisted laparoscopic pyeloplasty (RALP) has been increasingly utilized in the treatment of pediatric ureteropelvic junction obstruction (UPJO) with reported success rates of >95%. Complex renal anatomy can make some cases challenging to reconstruct. To evaluate outcomes of children undergoing RALP with aberrant renal anatomy and compare it to those with simple renal anatomy. An IRB approved prospective registry was queried to retrospectively identify all patients who underwent robotic pyeloplasty at our institution from 2012 to 2022. Patients undergoing re-do pyeloplasty were excluded. Complex anatomy was defined as horseshoe kidney, ectopic/pelvic kidney, duplex collecting system, fully bifid renal pelvis and severe malrotation (≥180°). A comparative analysis of baseline demographics, pre-operative clinical/radiological characteristics, intra and post-operative details, and long-term success was performed between those patients with complex anatomy and those without. Of 405 total robotic pyeloplasty's, 375 patients (378 total pyeloplasty; 353 simple, 22 complex) met inclusion criteria. 27 re-do were excluded from analysis. The complex pyeloplasty cohort included 9 horseshoe kidneys, 8 duplex collecting systems, 3 ectopic/pelvic kidneys and 2 kidneys with severe malrotation. There was no difference in age (58 vs 31 months; p=0.38), procedure time (203 vs 207min; p=0.06), length of stay (1.4 vs 1.3 days; p=0.99), or success (91.6% vs 100%; p=0.24) between the simple and complex groups. Etiology of obstruction differed significantly between groups - high insertion was more common (3.9% vs 18.2%, p=0.02) and intrinsic narrowing was less common (60.1% vs 36.4%, p=0.04) in patients with complex anatomy. A multivariate logistic regression was adjusted for age, gender, etiology of obstruction, preoperative differential renal function and post-operative complications and found no difference in success between complex and simple RALP. The findings showed no significant differences in age, procedure time, length of hospital stay, or success rates between the two groups. Specifically, the success rates were 91.6% for the complex group and 100% for the simple group (p=0.24), indicating comparable efficacy. However, the etiology of obstruction varied significantly, with high ureteral insertion more common in the complex anatomy group (18.2% vs. 3.9%, p=0.02) and intrinsic narrowing less common (36.4% vs. 60.1%, p=0.04). Despite these differences, multivariate logistic regression, adjusted for confounders, confirmed no difference in success rates between the groups. RALP is a safe and efficacious approach in patients with complex anatomy with success rates comparable to index patients. High ureteral insertion does appear to be more common in patients with complex anatomy undergoing pyeloplasty.

Preventable predictive factors of post-colonoscopy colorectal cancer in inflammatory bowel disease.

Post-colonoscopy colorectal cancer (PCCRC) is a colorectal cancer (CRC) diagnosed after a colonoscopy in which no cancer is detected (index colonoscopy). Although the overall cumulative rates of PCCRC are low in both the general population and inflammatory bowel disease (IBD) patients, the overall incidence of PCCRC in IBD is greater than that documented in the general population. This study aimed to identify the index colonoscopy-related factors and patients' characteristics influencing IBD-associated PCCRC development. We carried out an observational, retrospective study in which IBD-associated PCCRCs were diagnosed between 2010 and 2023. The PCCRC group was compared to a control cohort of IBD patients without CRC matched 1:1 by several demographic and clinical features as well as characteristics of index colonoscopy to minimize selection bias. Among 61 CRCs identified, 37 (61%) were PCCRC. Twelve of 37 (32%) PCCRC were diagnosed within 12 months after the previous negative colonoscopy, 15 (41%) within 12-36 months, and 10 (27%) within 36-60 months. In the multivariate analysis, the inadequate bowel preparation of the index colonoscopy (OR: 5.9; 95% CI: 11.1- 31.4) and the presence of high-risk factors for CRC (OR: 24.03; 95% CI: 3.1-187.8) were independently associated with PCCRC. Conversely, prior exposure to immunosuppressors/biologics (OR: 0.17; 95% CI: 0.03-0.83) and random biopsies sampling at index colonoscopy (OR:0.19; 95% CI: 0.04-0.85) were inversely associated with PCCRC. More than 50% of CRCs in our population were PCCRC. PCCRCs were associated with previous inadequate cleansing and occurred more frequently in high-risk patients.

Clinicopathologic and molecular study of superficial CD34-positive fibroblastic tumours mimicking atypical fibrous histiocytoma (dermatofibroma).

Superficial CD34-positive fibroblastic tumour (SCD34FT) is an uncommon but distinctive low-grade neoplasm of the skin and subcutis that shows frequent CADM3 expression by immunohistochemistry (IHC). In this study, prompted by an index case resembling 'atypical fibrous histiocytoma (FH)' that was positive for CADM3 IHC, we systematically examined a cohort of tumours previously diagnosed as 'atypical FH' by applying CADM3 and fluorescence in situ hybridization (FISH) for PRDM10 rearrangement, to investigate the overlap between these tumour types. Forty cases of atypical FH were retrieved, including CD34-positive tumours (n = 20) and CD34-negative tumours (n = 20). All tumours were stained for CADM3. All CADM3-positive tumours were evaluated by FISH to assess for PRDM10 rearrangement. Eleven CD34-positive tumours (11/20, 55%) coexpressed CADM3 and were reclassified as SCD34FT. None (0/20) of the CD34-negative atypical FH were CADM3-positive. Reclassified SCD34FT (10/11) arose on the lower extremity, with frequent involvement of the thigh (n = 8). Features suggestive of atypical FH were observed in many reclassified cases including variable cellularity, spindled morphology, infiltrative tumour margins, collagen entrapment, epidermal hyperpigmentation, and acanthosis. Variably prominent multinucleate giant cells, including Touton-like forms, were also present. An informative FISH result was obtained in 10/11 reclassified tumours, with 60% (6/10) demonstrating PRDM10 rearrangement. A significant subset of tumours that histologically resemble atypical FH, and are positive for CD34, coexpress CADM3 and harbour PRDM10 rearrangement, supporting their reclassification as SCD34FT. Awareness of this morphologic overlap and the application of CADM3 IHC can aid the distinction between SCD34FT and atypical FH.

Clinical laboratory test utilization of CSF oligoclonal bands and IgG index in a tertiary pediatric hospital

BackgroundCriteria developed for the diagnosis of multiple sclerosis (MS) in adults are also used in the pediatric setting. However, differential diagnosis in pediatric-onset MS (POMS) is distinct from that of adult-onset MS. There is little literature characterizing the utility of oligoclonal bands (OCB) and IgG index in differentiating POMS from other childhood diseases with overlapping clinical presentation which can require immediate treatment. MethodsA retrospective review of all MS panels resulted between March 2022 and May 2023 on patients age ≤ 18 years at one tertiary care pediatric hospital in the northeastern United States was performed with pediatric neurology collaboration to characterize clinical utility (n = 85 cases). ResultsDemyelinating diseases accounted for 31 of 85 total cases (36.5%), 12 of these cases were POMS (14%). Other diagnoses consisted of psychiatric etiologies (17.6%), infectious meningitis/encephalitis (5.9%), and migraine (5.9%). Elevated IgG index was seen in 67% of those with demyelinating diseases, versus only 13% of those with other conditions. Unique OCBs were found in 41% of those with demyelinating diseases, versus only 9% of those with other conditions. Fourteen of 15 patients (93.3%) with psychiatric conditions had normal MS panels. ConclusionsPatients with demyelinating diseases were more likely to have elevated IgG index and unique OCBs versus patients with other conditions. For pediatric hospitals without in-house OCB evaluation, implementation of an in-house IgG index may serve as a rapid screen for differentials that include demyelinating diseases while awaiting OCB results, in the appropriate clinical context. Impact statementIgG index and CSF oligoclonal bands are important tools in the diagnosis of patients with suspected Multiple Sclerosis (MS). In the pediatric population, these markers are used to differentiate pediatric-onset MS (POMS) from other neurologic, psychiatric, and inflammatory diseases that display clinical overlap. The use of these markers in differentiating these conditions has not been thoroughly investigated. We examined the associations between abnormal markers and final diagnoses in pediatric patients undergoing testing for POMS in order to identify trends that may enhance ordering and reporting practices.

Cerebral involvement in sitosterolemia

BackgroundSitosterolemia, an autosomal recessive condition, is characterized by impaired metabolism of plant sterols. Clinical symptoms include skin xanthoma, premature atherosclerotic disease, arthritis, and unexplained hematological abnormalities. However, there is a dearth of studies on sitosterolemia-related brain damage.MethodsThis study focused on the family of two sitosterolemia patients who presented with severe hypercholesterolemia and xanthoma. Radiological examinations, biopsies, whole-exome sequencing (WES), and plant sterol tests were conducted.ResultsThe index patient, a 66-year-old female, initially exhibited weakness in both lower limbs and later developed urinary and fecal incontinence. Neuroimaging showed that the falx of the brain had irregular fusiform thickening. Significant tissue edema was observed around the lesions in the bilateral frontal-parietal lobes. Pathological analysis of the biopsied brain lesion revealed extensive cholesterol crystal deposition and lymphocyte infiltration in the matrix. The index patient who experienced cerebral impairment and her sister both carried two compound heterozygous variants in ATP binding cassette transporter G5 (ABCG5). These included the nonsense variants NM_022436: c.751 C > T (p.Q251X) in exon 6 and NM_022436: c.1336 C > T (p.R446X) in exon 10. A notable increase in plant sterol levels was observed in the younger sister of the index patient.ConclusionThis study highlights a previously unreported neurological aspect of sitosterolemia. Imaging and pathology findings suggest that cholesterol crystals may be deposited in connective tissues such as the cerebral falx and pia mater through blood circulation.

Pediatric intramuscular hemangioma in the submandibular triangle and other musculoskeletal presentations: A pediatric case series

BackgroundIntramuscular hemangiomas (IMH) account for 0.8 % or less of all benign soft tissue tumors in the general population. Due to their uncommon nature, especially in the head and neck, they are often misdiagnosed and not included in the differential diagnosis. MethodsThis study describes a case series of eleven pediatric patients with a diagnosis of IMH through a retrospective review of the electronic health records and archival records in the Department of Pathology at Children's Hospital of Colorado (CHCO). ResultsThe index case had a unique presentation in the submandibular triangle, while the remaining ten cases are appendicular and thoracolumbar in nature. ConclusionsThis case series contributes to the sparse scientific literature available regarding IMH, particularly in its head and neck presentation as relevant to otolaryngologists.

Familial distribution of hepatitis B virus infection in Espirito Santo state, Brazil

To evaluate the familial distribution of hepatitis B virus (HBV), a retrospective analysis of medical records of patients treated in Vitória, Espírito Santo, Brazil, was performed. Patients with markers of HBV infection who had a family member with evidence of HBV infection were index cases of each family. Of the 65 index cases, 26 (40%) had chronic hepatitis (CH), 13 (20%) liver cirrhosis (LC), 4 (6.1%) hepatocellular carcinoma (HCC), 20 (30.8%) were inactive carriers and two (3.1%) had immunity after contact with HBV. Among 275 family members, 226 had evidence of HBV infection, 171 of which were HBsAg positive and 55 had previous contact and immunity. HBsAg was significantly higher in consanguineous than non-consanguineous relatives (170/244 and 1/31, respectively, p &lt;0.0001) and among siblings of index cases. There were 2 to 12 affected individuals per family, involving one, two, or three generations. In 14/65 families, two or more cases of LC, CH, or HCC were observed, compromising up to three generations. Results demonstrate familial clustering of HBV in Espírito Santo in up to three generations and familial aggregation of severe forms of the infection. Family investigation of HBV is important, allowing early diagnosis and treatment before progression to advanced forms of the disease. KEY WORDS: Chronic hepatitis; liver cirrhosis; hepatocellular carcinoma; viral transmission; familial aggregation.

Cardiomyopathies matter: a multistakeholder european initiative to improve patient outcomes through effective health policies

Abstract Background/Introduction Cardiomyopathies are common and affect up to 1:250 of the population. Despite conferring a risk for sudden cardiac death and substantial disease burdens that could be reduced through better awareness, detection and care, cardiomyopathy care is rarely incorporated in European and national health policies. New European Society of Cardiology cardiomyopathy guidelines (1) could substantially benefit care but need to be supported by effective policies. Cardiomyopathies Matter is a Europe-wide, multistakeholder initiative aiming to raise awareness about cardiomyopathies and to ensure they receive the policy attention they warrant from EU and national decision-makers. Methods Cardiomyopathies Matters participants include experts from the fields of cardiology, cardiac nursing, economics, and patient advocacy, coordinated by a Secretariat, representing 36 countries and 6 patient advocacy groups (PAGs). A Policy Roadmap and other publications were co-created based on i) reviews of published and grey literature, and ii) input from topic experts and PAGs through 2 group workshops, individual consultation meetings, and a modified nominal group technique reviewing successive drafts toward consensus approval. Results The Roadmap (2) identifies unmet needs and challenges throughout the patient care pathway and offers holistic EU and national policy recommendations to address these and improve patient outcomes (Figure 1). These include policy measures to support early and accurate diagnosis, access to expert multidisciplinary care, guidelines-informed disease investigation and management, holistic support and empowerment of patients and carers, and research and innovation. Key aspects for nurses and allied health professionals include the need for 1)improved knowledge and awareness to promote early diagnosis; 2)rapid referral systems to multidisciplinary care and access to specialist cardiomyopathy or heart failure nurses care coordination, 3)genetic counselling (index cases and cascade/family screening), and 4)support of patients and families. Building on existing examples of good practice at national expert centre networks (e.g. France, Spain, UK),Cardiomyopathies Matter published updated policy recommendations for the European Union mandate (3), which are now being adopted more widely. National initiatives are underway or in development in Belgium, Hungary, Italy, Netherlands, Poland, and Spain. Local actions include multistakeholder roundtables and events, national Roadmap publications, events, educational activities, and media outreach. Conclusions EU and national Cardiovascular Health Action Plans are needed, with specific attention to cardiomyopathies and other inherited CVDs. Cardiomyopathies Matter fosters collaboration between healthcare professionals, PAGs and policymakers to promote policies that ensure all patients and families have access to guidelines-informed care.Figure 1Cardiomyopathy Priorities

Clinical and molecular characterization of limb-girdle muscular dystrophy 2G/R7 in a large cohort of Brazilian patients.

Limb-girdle muscular dystrophy type 2G/R7 (LGMD2G/R7) is an ultra-rare condition initially identified within the Brazilian population. We aimed to expand clinical and genetic information about this disease, including its worldwide distribution. A multicenter historical cohort study was performed at 13 centers in Brazil in which data from index cases and their affected relatives from consecutive families with LGMD2G/R7 were reviewed from July 2017 to August 2023. Additionally, a systematic literature review was conducted to identify case reports and series of the disease worldwide. Forty-one LGMD2G/R7 cases were described in the Brazilian cohort, being all subjects homozygous for the c.157C>T/(p.Gln53*) variant in TCAP. Survival curves showed that the median disease duration before individuals required walking aids was 21 years. Notably, women exhibited a slower disease progression, requiring walking aids 13 years later than men. LGMD2G/R7 was frequently reported not only in Brazil but also in China and Bulgaria, with 119 cases identified globally, with possible founder effects in the Brazilian, Eastern European, and Asian populations. These findings are pivotal in raising awareness of LGMD2G/R7, understanding its progression, and identifying potential modifiers. This can significantly contribute to the development of future natural history studies and clinical trials for this disease.

A prospective randomised controlled trial investigating household SARS-CoV-2 transmission in a densely populated community in Cape Town, South Africa – the transmission of COVID-19 in crowded environments (TRACE) study

BackgroundSouth Africa’s first SARS-CoV-2 case was identified 5th March 2020 and national lockdown followed March 26th. Households are an important location for secondary SARS-CoV-2 infection. Physical distancing and sanitation – infection mitigation recommended by the World Health Organization (WHO) at the time – are difficult to implement in limited-resource settings because of overcrowded living conditions.MethodsThis study (ClinicalTrials.gov NCT05119348) was conducted from August 2020 to September 2021 in two densely populated, low socioeconomic Cape Town community sub-districts. New COVID-19 index cases (ICs) identified at public clinics were randomised to an infection mitigation intervention (STOPCOV) delivered by lay community health workers (CHWs) or standard of care group. STOPCOV mitigation measures included one initial household assessment conducted by a CHW in which face masks, sanitiser, bleach and written information on managing and preventing spread were provided. This was followed by regular telephonic follow-up from CHWs. SARS-CoV-2 PCR and IgM/IgG serology was performed at baseline, weeks 1, 2, 3 and 4 of follow-up.ResultsThe study randomised 81 ICs with 245 HHCs. At baseline, no HHCs in the control and 7 (5%) in the intervention group had prevalent SARS-CoV-2. The secondary infection rate (SIR) based on SARS-CoV-2 PCR testing was 1.9% (n = 2) in control and 2.9% (n = 4) in intervention HHCs (p = 0.598). At baseline, SARS-CoV-2 antibodies were present in 15% (16/108) of control and 38% (52/137) of intervention participants. At study end incidence was 8.3% (9/108) and 8.03% (11/137) in the intervention and control groups respectively. Antibodies were present in 23% (25/108) of control HHCs over the course of the study vs. 46% (63/137) in the intervention arm. CHWs made twelve clinic and 47 food parcel referrals for individuals in intervention households in need.DiscussionParticipants had significant exposure to SARS-CoV-2 infections prior to the study. In this setting, household transmission mitigation was ineffective. However, CHWs may have facilitated other important healthcare and social referrals.

Genetic Analysis of 252 Index Cases with Inherited Retinal Diseases Using a Panel of 351 Retinal Genes.

Inherited retinal diseases (IRDs) are extremely heterogeneous with at least 350 causative genes, complicating the process of genetic diagnosis. We analyzed samples of 252 index cases with IRDs using the Blueprint Genetics panel for "Retinal Dystrophy" that includes 351 genes. The cause of disease could be identified in 55% of cases. A clear difference was obtained between newly recruited cases (74% solved) and cases that were previously analyzed by panels or whole exome sequencing (26% solved). As for the mode of inheritance, 75% of solved cases were autosomal recessive (AR), 10% were X-linked, 8% were autosomal dominant, and 7% were mitochondrial. Interestingly, in 12% of solved cases, structural variants (SVs) were identified as the cause of disease. The most commonly identified genes were ABCA4, EYS and USH2A, and the most common mutations were MAK-c.1297_1298ins353 and FAM161A-c.1355_1356del. In line with our previous IRD carrier analysis, we identified heterozygous AR mutations that were not the cause of disease in 36% of cases. The studied IRD panel was found to be efficient in gene identification. Some variants were misinterpreted by the pipeline, and therefore, multiple analysis tools are recommended to obtain a more accurate annotation of potential disease-causing variants.