Index Case Research Articles

Tuberculosis preventive treatment among the household contacts of tuberculosis patients – Coverage and correlates in a block of Murshidabad district, West Bengal: A cross-sectional study

BackgroundIndia started implementing tuberculosis preventive treatment (TPT) among all household contacts of Tuberculosis (TB) cases, as a globally accepted strategy for elimination of TB. ObjectivesWe aimed to assess the extent of TPT coverage and adherence; ascertain the reasons for non-initiation and non-adherence; and to determine the correlates of coverage. MethodsWe conducted a cross-sectional study in a block of Murshidabad district, West Bengal during September–November’2023. A calculated sample of 301 eligible household contacts of ‘index cases’ (microbiologically-confirmed drug-sensitive pulmonary TB) registered during October’22 to March’23 were studied. We interviewed the participants/respondents with pre-designed schedule and prior informed consent. Descriptive and inferential statistics were applied through Statistical Package for Social Sciences (version 20). ResultsOf 301 contacts, 179(59.5%) individually traced/counseled at the household; 238 (79.1%) were screened for TB symptoms. TPT initiation was 74.8% (225/301) with 47.1% within seven days of treatment initiation of index case; TPT not offered by health personnel (59.2%) being major reason for non-initiation. Completion rate with adherence to full course was 69.3% (156/225); perceived lack of need (50.7%) and migration (21.7%) being major reasons for non-adherence. Overall coverage of full course TPT among total eligible contacts was only 51.8% (156/301). On multivariable logistic regression; male gender (aOR = 1.982; 95% CI = 1.004–3.915), contacts with individual tracing/counseling (aOR = 13.507; 95% CI = 6.781–26.906) and who had symptoms screening (aOR = 5.694; 95% CI = 2.223–14.587) predicted significantly higher TPT coverage. ConclusionCascade of care indicators for TPT remains suboptimal in the area and indicates need for further strengthening of programmatic aspects of its implementation.

Asymptomatic Children as a Missing Link in Preventing COVID-19 Transmission.

Investigating the prevalence of the coronavirus disease 2019 (COVID-19) infection in asymptomatic children who have been in close contact with symptomatic individuals is instrumental for refining public health approaches, protecting vulnerable populations, and mitigating the broader impact of the pandemic. Accordingly, this study aimed to evaluate the incidence of COVID-19 infection in asymptomatic children who had been in close contact with parents exhibiting COVID-19 symptoms. Study Design: A cross-sectional study. The present cross-sectional study was conducted on 175 asymptomatic children who had been in close contact with COVID-19 confirmed cases in Hamadan County from March 2021 to August 2021. Reverse transcription polymerase chain reaction (RT-PCR) testing was performed on all asymptomatic children who had been in close contact with an individual with COVID-19. Furthermore, multiple logistic regressions were conducted to determine the predictors of COVID-19 transmission from family members to children. Out of the 175 children in close contact with index cases, 53 (30.29%) tested positive for COVID-19 through PCR. Regarding factors related to the index case, male cases (Adjusted odds ratio [AOR]=2.29; 95% confidence interval [CI]: 1.03-5.09, P=0.041), rural dwellers (AOR=3.22; 95% CI: 1.02-10.16, P=0.046), illiterate cases (AOR=8.45; 95% CI: 1.76-40.65, P=0.008), and cases presenting with nasal congestion symptoms (AOR=9.12; 95% CI: 2.22-37.40, P=0.002) were more prone to transmitting the virus to children who had close contact with them. The findings of the present study suggested that asymptomatic COVID-19 infection in household contacts is significant in children who were in close contact with a COVID-19-positive patient. Therefore, it is crucial to continue to monitor this group closely.

Post-exposure prophylaxis in leprosy (PEOPLE): a cluster randomised trial.

Post-exposure prophylaxis (PEP) using single-dose rifampicin reduces progression from infection with Mycobacterium leprae to leprosy disease. We compared effectiveness of different administration modalities, using a higher (20 mg/kg) dose of rifampicin-single double-dose rifampicin (SDDR)-PEP. We did a cluster randomised study in 16 villages in Madagascar and 48 villages in Comoros. Villages were randomly assigned to four study arms and inhabitants were screened once a year for leprosy, for 4 consecutive years. All permanent residents (no age restriction) were eligible to participate and all identified patients with leprosy were treated with multidrug therapy (SDDR-PEP was provided to asymptomatic contacts aged ≥2 years). Arm 1 was the comparator arm, in which no PEP was provided. In arm 2, SDDR-PEP was provided to household contacts of patients with leprosy, whereas arm 3 extended SDDR-PEP to anyone living within 100 m. In arm 4, SDDR-PEP was offered to household contacts and to anyone living within 100 m and testing positive to anti-phenolic glycolipid-I. The main outcome was the incidence rate ratio (IRR) of leprosy between the comparator arm and each of the intervention arms. We also assessed the individual protective effect of SDDR-PEP and explored spatial associations. This trial is registered with ClinicalTrials.gov, NCT03662022, and is completed. Between Jan 11, 2019, and Jan 16, 2023, we enrolled 109 436 individuals, of whom 95 762 had evaluable follow-up data. Our primary analysis showed a non-significant reduction in leprosy incidence in arm 2 (IRR 0·95), arm 3 (IRR 0·80), and arm 4 (IRR 0·58). After controlling for baseline prevalence, the reduction in arm 3 became stronger and significant (IRR 0·56, p=0·0030). At an individual level SDDR-PEP was also protective with an IRR of 0·55 (p=0·0050). Risk of leprosy was two to four times higher for those living within 75 m of an index patient at baseline. SDDR-PEP appears to protect against leprosy but less than anticipated. Strong spatial associations were observed within 75 m of index patients. Targeted door-to-door screening around index patients complemented by a blanket SDDR-PEP approach will probably have a substantial effect on transmission. European and Developing Countries Clinical Trials Partnership. For the French translation of the abstract see Supplementary Materials section.

Changing epidemic of tuberculosis amidst the COVID-19 pandemic in the Western Pacific Region: analysis of tuberculosis case notifications and treatment outcomes from 2015 to 2022

Coronavirus disease-2019 (COVID-19) pandemic has deeply impacted tuberculosis (TB) services globally. This study aims to assess the COVID-19 pandemic's impact on TB diagnosis and care and explore associated factors in the Western Pacific Region. We analysed TB case notifications and treatment outcomes for the Region and 14 selected countries and areas from 2015 to 2022. We further explored differences in reported cases from predicted cases by the UHC service coverage index and Human Development Index (HDI), and the relationship between the Stringency Index and TB case notifications during the pandemic. TB case notifications declined in 2020 (21%) and 2021 (23%) compared to predicted cases and partly recovered in 2022 (18%). The shortfalls in 2020 and 2021 were more prominent in priority countries with high TB burden, where the decrease in clinically diagnosed pulmonary cases and paediatric cases was particularly pronounced. In priority countries, TB case notifications have a positive relationship with UHC service coverage index and HDI in 2021 and an inverse relationship with Stringency Index during the pandemic. In contrast, treatment outcomes have not changed significantly due to the pandemic across countries in the Region. The COVID-19 pandemic has adversely impacted TB diagnosis and care in the Western Pacific Region, especially TB case detection. Stringent government policies against the pandemic, coupled with weak health systems and suboptimal socio-economic development, may have brought a more profound and prolonged impact in priority countries. The Korea Disease Control and Prevention Agency and the Japan Ministry of Health, Labour and Welfare.

Impact of staffing an inpatient oncology consult service with dedicated hospital-based oncologists.

e13538 Background: No standard care model for hospitalized patients with cancer currently exists. The majority of oncology care is provided in the outpatient setting. Consequently, for many oncologists, inpatient care is a secondary responsibility. To address this issue, several U.S. institutions have changed their inpatient oncology models to include dedicated inpatient oncology-trained attendings (hospital-based oncologists). In this study, we investigate outcomes following such a change on an inpatient solid oncology consult service. Methods: This is a single-institution retrospective study of the University of California, San Francisco (UCSF)’s inpatient solid oncology consult service, which switched from a rotating outpatient oncologist attending model to a dedicated inpatient oncologist model in 2018. Since data prior to the switch were not available, we compared all inpatients who received an oncology consult (n=3974) with a comparison group (CG) of all inpatients with a solid tumor diagnosis who did not receive an oncology consult (n=3200) between fiscal years 2018 and 2023. We analyzed trends in case mix index (case complexity), in-hospital mortality index (observed/expected), 30-day unplanned readmission rate, length of stay index, and direct cost index using the Pearson correlation coefficient. In 2022, we conducted an anonymous retrospective pre/post-switch survey of hospitalists who had worked on the hospital medicine service both before and after the switch and compared mean satisfaction with oncology consultation (5-point scale) using Student’s t test. Results: Following the switch, the number of weeks per year covered by dedicated inpatient oncologists increased from seven (2018) to 39 (2023) out of 52. From 2018 to 2023, we found a significant increase in annual consults (495 to 919, r=0.95, p<0.01) and case mix index (2.30 to 3.30, r=0.90, p=0.01; CG 1.60 to 1.70, r=0.60, p=0.20), and a significant decrease in mortality index (1.59 to 0.70, r=-0.98, p<0.01; CG 0.90 to 0.48, r=-0.66, p=0.15). There were non-significant decreases in 30-day unplanned readmission rate (35.8% to 30.5%, r=-0.77, p=0.07), length of stay index (1.45 to 1.32, r=-0.75, p=0.08), and direct cost index (2.2 to 1.8, r=-0.61, p=0.20), similar to the CG. Mean (standard deviation) satisfaction increased from 3.27 (1.22) pre-switch to 4.53 (0.92) post-switch ( p=0.02, response rate 15/51, 29%). Conclusions: Switching to a dedicated inpatient oncologist model on a consult service was associated with decreased in-hospital mortality and increased satisfaction with oncology consultation despite growing case volume and complexity, while readmission rate, length of stay, and cost remained unchanged. This study adds to growing literature supporting dedicated inpatient oncologist attending models of care and is in line with recent literature from other specialties supporting similar inpatient care models.

Cochlear Implantation in Patients With Osteolytic Labyrinthitis: A Case Series.

To describe the rare process of osteolytic labyrinthitis, previously referred to as labyrinthine sequestrum, which involves progressive obliteration of the bony and membranous labyrinth with eventual supplantation with soft tissue and, in some cases, bony sequestrum. Three patients with diverse presentations of osteolytic labyrinthitis from two tertiary care academic medical centers. Case series report analyzing the relevant clinical, radiologic, pathologic, and surgical data on our patients with osteolytic labyrinthitis and comparing these index cases to the existing literature. We describe the varying image findings seen in osteolytic labyrinthitis on computed tomography and magnetic resonance imaging. Also, we report successful surgical intervention and hearing rehabilitation with cochlear implantation in patients with osteolytic labyrinthitis. Our three patients presented with profound sudden sensorineural hearing loss and vertigo consistent with labyrinthitis. None of the three patients had a history of chronic otitis media. Imaging workup revealed varying degrees of erosion to the otic capsule bone demonstrating the spectrum of disease seen in osteolytic labyrinthitis. Although two cases showed osteolytic changes to the semicircular canals and vestibule, the first case revealed frank bony sequestrum within the obliterated labyrinth. The three cases were taken for surgical debridement and cochlear implantation. We propose the new term, osteolytic labyrinthitis-previously referred to as labyrinthine sequestrum-to describe the rare spectrum of disease characterized by destruction of the osseous and membranous labyrinth and potential supplantation with bony sequestrum. Cochlear implantation is a viable option in selected patients with osteolytic labyrinthitis.

Trends in Index Case Load and Case Variety in Training Institutions Accredited by the Philippine Society of General Surgeons: A 10-Year Review (2009-2018)

Trends in Index Case Load and Case Variety in Training Institutions Accredited by the Philippine Society of General Surgeons: A 10-Year Review (2009-2018)

Resurgence of seasonal influenza driven by A/H3N2 and B/Victoria in succession during the 2023-2024 season in Beijing showing increased population susceptibility.

During the COVID-19 pandemic, non-pharmaceutical interventions were introduced to reduce exposure to respiratory viruses. However, these measures may have led to an "immunity debt" that could make the population more vulnerable. The goal of this study was to examine the transmission dynamics of seasonal influenza in the years 2023-2024. Respiratory samples from patients with influenza-like illness were collected and tested for influenza A and B viruses. The electronic medical records of index cases from October 2023 to March 2024 were analyzed to determine their clinical and epidemiological characteristics. A total of 48984 positive cases were detected, with a pooled prevalence of 46.9% (95%CI 46.3-47.5). This season saw bimodal peaks of influenza activity, with influenza A peaked in week 48, 2023, and influenza B peaked in week 1, 2024. The pooled positive rates were 28.6% (95%CI 55.4-59.6) and 18.3% (95%CI 18.0-18.7) for influenza A and B viruses, respectively. The median values of instantaneous reproduction number were 5.5 (IQR 3.0-6.7) and 4.6 (IQR 2.4-5.5), respectively. The hospitalization rate for influenza A virus (2.2%, 95%CI 2.0-2.5) was significantly higher than that of influenza B virus (1.1%, 95%CI 0.9-1.4). Among the 17 clinical symptoms studied, odds ratios of 15 symptoms were below 1 when comparing influenza A and B positive inpatients, with headache, weakness, and myalgia showing significant differences. This study provides an overview of influenza dynamics and clinical symptoms, highlighting the importance for individuals to receive an annual influenza vaccine.

Identification and correction for collider bias in a genome-wide association study of diabetes-related heart failure

Type 2 diabetes (T2D) is a major risk factor for heart failure (HF) and has elevated incidence among individuals with HF. Since genetics and HF can independently influence T2D, collider bias may occur when T2D (i.e., collider) is controlled for by design or analysis. Thus, we conducted a genome-wide association study (GWAS) of diabetes-related HF with correction for collider bias. We first performed a GWAS of HF to identify genetic instrumental variables (GIVs) for HF and to enable bidirectional Mendelian randomization (MR) analysis between T2D and HF. We identified 61 genomic loci, significantly associated with all-cause HF in 114,275 individuals with HF and over 1.5 million controls of European ancestry. Using a two-sample bidirectional MR approach with 59 and 82 GIVs for HF and T2D, respectively, we estimated that T2D increased HF risk (odds ratio [OR] 1.07, 95% confidence interval [CI] 1.04-1.10), while HF also increased T2D risk (OR 1.60, 95% CI 1.36-1.88). Then we performed a GWAS of diabetes-related HF corrected for collider bias due to the study design of index cases. After removing the spurious association of TCF7L2 locus due to collider bias, we identified two genome-wide significant loci close to PITX2 (chromosome 4) and CDKN2B-AS1 (chromosome 9) associated with diabetes-related HF in the Million Veteran Program and replicated the associations in the UK Biobank. Our MR findings provide strong evidence that HF increases T2D risk. As a result, collider bias leads to spurious genetic associations of diabetes-related HF, which can be effectively corrected to identify true positive loci.

Modeling Extraordinary Response Through Targeting Secondary Alterations in Fusion-Associated Sarcoma.

Targeted therapy in translocation-associated sarcomas has been limited to oncogenic activation of tyrosine kinases or ligands while gene fusions resulting in aberrant expression of transcription factors have been notoriously difficult to target. Moreover, secondary genetic alterations in sarcomas driven by translocations are uncommon, comprising mostly alterations in tumor suppressor genes (TP53, CDKN2A/B). Our study was triggered by an index patient showing a dramatic clinical response by targeting the secondary BRAF V600E mutation in a metastatic angiomatoid fibrous histiocytoma (AFH) harboring the typical EWSR1::CREB1 fusion. The patient, a 28-year-old female, was diagnosed with an AFH of the thigh and followed a highly aggressive clinical course, with rapid multifocal local recurrence within a year and widespread distant metastases (adrenal, bone, liver, lung). The tumor showed characteristic morphologic features, with histiocytoid cells intermixed with hemorrhagic cystic spaces and lymphoid aggregates. In addition to the pathognomonic EWSR1::CREB1 fusion, targeted DNA sequencing revealed in both primary and adrenal metastatic sites a hot spot BRAF V600E mutation and a CDKN2A/B deletion. Accordingly, the patient was treated with a BRAF-MEK inhibitor combination (encorafenib/binimetinib) showing an excellent but short-lived response. Using a CRISPR-Cas9 approach, we introduced the BRAF c.1799 T>A point mutation in human embryonic stem (hES) cells harboring a conditional EWSR1 (exon7)::CREB1 (exon7) translocation and further differentiated to mesenchymal progenitors (hES-MP) before fusion expression. The cells maintained the fusion transcript expression and the AFH core gene signature while responding to treatment with encorafenib and binimetinib. These results highlight that additional targeted DNA NGS in chemotherapy-resistant translocation-associated sarcomas may reveal actionable oncogenic drivers occurring as secondary genetic events during disease progression.

Household Transmission and Clinical Features of SARS-CoV-2-Positive and -Negative Respiratory Tract Infections.

Comparative data on the transmission of respiratory infections positive and negative for SARS-CoV-2 in households with children are limited. In June-August 2020, we recruited 700 participants (175 households, 376 children, 324 adults) to be prospectively followed for all respiratory tract infections. Follow-up lasted from recruitment till April 2022. Daily symptoms were monitored by weekly electronic questionnaires. SARS-CoV-2 PCR testing from nasopharyngeal specimens was performed for symptomatic participants and twice (one-week interval) for the household members of positive participants. Clinical features and secondary attack rates (SARs), based on the onset of symptoms, were compared between SARS-CoV-2-positive and -negative respiratory infections. Most (90%) SARS-CoV-2 infections occurred from January to April 2022 when Omicron BA.1 and BA.2 were the dominant variants. SARS-CoV-2-positive infections were transmitted more often than SARS-CoV-2-negative infections (SAR, 41% vs 24%; P < .001). SARS-CoV-2 transmission was similar for child and adult index cases (SAR, 40% vs 43%; P = .47), but the transmission of SARS-CoV-2-negative infections was higher for child index cases (SAR, 27% vs 18%; P < .001). Our findings demonstrate that SARS-CoV-2 Omicron viruses spread more effectively within households compared to other respiratory infections.

Digital interventions for STI and HIV partner notification: a scoping review

BackgroundPartner notification (PN) is key to the control of sexually transmitted infections (STIs) and human immunodeficiency virus (HIV). Digital interventions have been used to facilitate PN. A scoping review was...

Pheochromocytoma/paraganglioma type 5 syndrome as a cause of secondary hypertension in a Colombian patient: case report

Pheochromocytoma is a tumor derived from neural crest cells able to produce sympathomimetic substances and, hence, a particular clinical picture. It is responsible for less than 1% of high blood pressure cases, with an estimated incidence between 0.4 and 0.6 cases per 100,000 people each year, and an average survival of seven years. Pheochromocytoma is a solid tumor with a high genetic component, as heritability can reach 40%. Once diagnosed, its treatment and prognosis are partly conditioned by the associated pathogenic variants that can be documented, especially those related to RET, SDHx, VHL, and NF1 genes. We present the case of a young woman with abdominal pain and high blood pressure, who was found to have a pheochromocytoma. Genetic testing detected a rare and recently discovered pathogenic variant: the SDHA:c.1A>C (p.Met1Leu). The patient responded adequately to the surgical treatment and continued the follow-up without documented recurrences. The diagnostic approach for pheochromocytoma patients must start with a clinical suspicion, followed by metabolite measurement in blood and urine, and finally, imaging. Currently, technology development allows precision medicine applicability. In this case of pheochromocytoma, recent developments in precision medicine resulted in the detection of associated genetic components involving the patient and her family. Adequate screening of the index patient is required for documenting pathogenic variants and better characterizing the disease.

Genetic predisposition to pheochromocytoma and paraganglioma: 21 years of experience in the field

ContextPheochromocytoma and paraganglioma (PPGL) are rare neuroendocrine tumors with high heritability, justifying systematic genetic screening for a germline variant in one of the twenty predisposing genes described to date. PurposeTo describe the experience of one endocrine oncogenetic laboratory over a period of 21 years (2001–2022), from the beginning of PPGL genotyping with Sanger sequencing in 2001 to the implementation of next-generation sequencing (NGS). MethodThe activity database of an academic oncogenetic laboratory was searched to extract patients/relatives identified with a pathogenic variant/likely pathogenic variant (PV/LPV) over a period of 21 years. Clinical and genetic data were compared. ResultsIn total, 606 index cases with PPGL and 444 relatives were genotyped. Genotyping of index cases was performed by Sanger sequencing and gene deletion analysis in 327 cases and by NGS in 279. Germline PV/LPV spanning 10 genes was identified in 165 index cases (27.2%). Several recurrent PV/LPVs in SDHx were observed in non-related index cases, the most frequent being SDHD, c.170-1G>T (n=28). This subgroup showed great phenotypic variability both between and within families in terms of both tumor location and number. Four patients (1.1%) with PV/LPV in SDHx had 3PA (Pituitary Adenoma and pheochromocytoma/paraganglioma) syndrome. 258 relatives (58.1%) had inherited a PV/LPV in one driver gene. The rate of PV/LPV carriers who were symptomatic at first imaging evaluation was 32%, but varied between<20% in SDHB and SDHC and >50% in SDHD, VHL and MAX. ConclusionOur experience confirmed previously established genotype-phenotype correlations, but also highlights atypical clinical presentations, even for the same genetic variant. These data must be taken into account for optimal patient follow-up and management.

Homophily and social mixing in a small community: Implications for infectious disease transmission.

Community mixing patterns by sociodemographic traits can inform the risk of epidemic spread among groups, and the balance of in- and out-group mixing affects epidemic potential. Understanding mixing patterns can provide insight about potential transmission pathways throughout a community. We used a snowball sampling design to enroll people recently diagnosed with SARS-CoV-2 in an ethnically and racially diverse county and asked them to describe their close contacts and recruit some contacts to enroll in the study. We constructed egocentric networks of the participants and their contacts and assessed age-mixing, ethnic/racial homophily, and gender homophily. The total size of the egocentric networks was 2,544 people (n = 384 index cases + n = 2,160 recruited peers or other contacts). We observed high rates of in-group mixing among ethnic/racial groups compared to the ethnic/racial proportions of the background population. Black or African-American respondents interacted with a wider range of ages than other ethnic/racial groups, largely due to familial relationships. The egocentric networks of non-binary contacts had little age diversity. Black or African-American respondents in particular reported mixing with older or younger family members, which could increase the risk of transmission to vulnerable age groups. Understanding community mixing patterns can inform infectious disease risk, support analyses to predict epidemic size, or be used to design campaigns such as vaccination strategies so that community members who have vulnerable contacts are prioritized.

30years of prophylactic thyroidectomy for hereditary medullary thyroid cancer : Amilestone in translational medicine

Medullary thyroid cancer (MTC) is the most frequent manifestation of multiple endocrine neoplasia type 2 (MEN2) that determines the oncological outcome. Germline mutations in the rearranged during transfection (RET) protooncogene, atumor suppressor gene on chromosome 10q11.2, were identified 30 years ago as the genetic basis of MEN2 and published in 1993 and 1994. These seminal findings gave rise to the concept of prophylactic thyroidectomy for asymptomatic gene mutation carriers based on apositive RET gene test, which has become the standard of care ever since. Clinical genetic investigations showed genotype-phenotype correlations with respect to the individual gene mutation regarding the penetrance and onset of MTC and to alesser extent also with respect to the other components of MEN2, pheochromocytoma and primary hyperparathyroidism. From this a clinically relevant risk stratification could be derived. Initially, the optimal timing of prophylactic thyroidectomy was primarily based on the RET genotype alone, which was not sufficient for a precise age recommendation and subsequently required additional consideration of calcitonin serum levels for fine tuning. Calcitonin levels first show the risk of lymph node metastasis when they exceed the upper normal limit of the assay independent of carrier age and RET mutation. Routine calcitonin screening of patients with nodular thyroid disease, screening of families on identification of MEN2 index patients, and pre-emptive thyroidectomy in carriers of gene mutations with normal calcitonin levels have led to the fact that nowadays, 30years after the first description of the gene mutations causing the disease, the life-threatening hereditary MTC has become curable: ashining example for the success of translational transnational medical research for the benefit of patients.

Unveiling the Current Understanding of Idiopathic Spinal Cord Herniation: A Systematic Review.

Idiopathic spinal cord herniation (ISCH) is a rare condition that is characterized by ventral herniation of the spinal cord through a defect in the dura mater into the epidural space, with no identifiable cause. ISCH is frequently underdiagnosed, and the information available in case reports is limited. To provide an overview of the clinical manifestations and diagnosis of this condition, this study aims to conduct a review of reported cases of ISCH. A literature review was carried out using seven databases. The search was conducted using the keywords "Idiopathic spinal cord herniation" OR "Idiopathic Ventral Spinal Cord Herniation" AND "Case report" OR "case series." A total of 92 relevant papers reporting 224 cases, besides the index case, were determined. Of the cases, 58.5% were females and the mean age was 50.7 (SD 13.2) years. Symptoms, diagnoses, and outcomes were similar between genders. The most common clinical signs included motor symptoms (82.6%), instability (61.3%), hypoesthesia (59.2%), and disturbance of thermal sensitivity (47.3%). Brown-Séquard syndrome was observed in 27.2% of the cases, and surgical treatment was employed in 89.7% of the cases. ISCH is a pathology that is principally treated with surgical approach. This study provides valuable insights into the clinical manifestations and diagnosis of ISCH, which can aid in the early recognition and treatment of this rare condition.

Characteristics and outcomes associated with sarcomere mutations in patients with hypertrophic cardiomyopathy: A systematic review and meta-analysis

BackgroundHypertrophic cardiomyopathy (HCM) is an inherited heart disease that can lead to sudden cardiac death. Impact of genetic testing for the prognosis and treatment of patients with HCM needs to be improved. We conducted a systematic review and meta-analysis to investigate the characteristics and outcomes associated with sarcomere genotypes in index patients with HCM. MethodsA systematic search was conducted in Medline, Embase, and Cochrane Library up to Dec 31, 2023. Data on clinical characteristics, morphological and imaging features, outcomes and interventions were collected from published studies and pooled using a random-effects meta-analysis. ResultsA total of 30 studies with 10,825 HCM index patients were included in the pooled analyses. The frequency of sarcomere genes in HCM patients was 41%. Sarcomere mutations were more frequent in women (p < 0.00001), and were associated with lower body mass index (26.1 ± 4.7 versus 27.5 ± 4.3; p = 0.003) and left ventricular ejection fraction (65.7% ± 10.1% vs. 67.1% ± 8.6%; p = 0.03), less apical hypertrophy (6.5% vs. 20.1%; p < 0.0001) and left ventricular outflow tract obstruction (29.1% vs. 33.2%; p = 0.03), greater left atrial volume index (43.6 ± 21.1 ml/m2 vs. 37.3 ± 13.0 ml/m2; p = 0.02). Higher risks of ventricular tachycardia (23.4% vs. 14.1%; p < 0.0001), syncope (18.3% vs. 10.9%; p = 0.01) and heart failure (17.3% vs. 14.6%; p = 0.002) were also associated with sarcomere mutations. ConclusionsSarcomere mutations are more frequent in women, and are associated with worse clinical characteristics and poor outcomes.

Scrotal calcinosis cutis an unrelated finding in benign prostatic hyperplasia patient, is treatment sine qua non? A case report

Calcinosis cutis is a reactive and nonmalignant lesion characterized by solitary or multiple cutaneous nodules that can affect different parts of the body including the scrotum among other structures. Treatment is often sought because of cosmesis, itching, or pain. Despite this, it remains unclear or unimaginable why patients will be reluctant to accept treatment in the face of disfigurement. Several reasons have been documented, but the fear of genital mutilation from open surgical intervention is an unfamiliar reason advanced by the index case for declining open surgical intervention. Its diagnosis requires careful clinical evaluation and is confirmed by lesional biopsy for histological confirmation. This is a case of a 50-year-old trader who presented to our facility with a 35-year history of multiple, painless scrotal nodules and difficulty in passing urine for six months’ duration. He was diagnosed with benign prostatic hyperplasia (BPH) with the indication for surgical therapy and idiopathic scrotal calcinosis cutis. He consented and had endoscopic therapy for benign prostatic hyperplasia (BPH) but was reluctant to open surgical intervention for idiopathic scrotal calcinosis cutis despite disfigurement because of the fear of genital mutilation. The current treatment options include follow-up observation, medications, cryotherapy, laser, and surgical excision, depending on the patient’s choice, availability, and surgical expertise. The surgical option is often favored and encouraged due to its associated reduced chances of recurrence. Therefore, it is pertinent to respect the patient’s opinion and should override other considerations in clinical practice. The lesson herein can assist other clinicians in avoiding justifiable medical litigations, hence, the need for this case report and a review of the literature.

Current real-world evidence of genetic testing diagnostic yield in a large cohort of long QT syndrome

Abstract Background Diagnostic yield in long QT syndrome (LQTS) ranges between 30-70%, depending on the studied population. LQTS can lead to an unexpected sudden cardiac death. For this reason and due to its wider current availability, genetic testing in patients with suspicion of LQTS has spread. Purpose The aim of this study is to investigate the genetic testing yield among a large cohort of heterogeneous index cases with LQTS phenotype. Methods Diagnostic yield was restrospectively evaluated in a cohort of index cases referred to our laboratory for genetic study with LQTS phenotype. Genetic study was performed with customized libraries through next generation sequencing (NGS), which included copy number variations (CNVs) analysis. Patients with LQTS phenotype studied both with "long QT panels" and with broader cardiovascular panels were included, but those with additional cardiac phenotype (cardiomyopathies, heart defects or catecholaminergic polymorphic ventricular tachycardia) were excluded. Positive genetic reports were considered when a likely pathogenic (LP) or pathogenic (P) variant could explain patient´s phenotype. Inconclusive reports were described when a variant considered risk factor (RF) or a variant of uncertain significance variant (VUS) or a hot-VUS was identified in a clinically relevant gene. Results 1183 index cases were genotyped for LQTS phenotype. Only 164 index cases (13,8%) were studied with broader panels which included between 77 and 368 genes. The rest (n=1019) were studied with LQTS panels (either with small panels which included KCNQ1, KCNH2, KCNE1, KCNE2, SCN5A, KCNJ2, CACNA1C and with up to 36 genes-QT panels). Around 27% (n=321) of the index cases had a positive result. They carried LP/P variants in the following genes: KCNQ1 (n=166, 52%), KCNH2 (n=112), SCN5A (n=25), RYR2 (n=5), CACNA1C (n=3), HCN4 (n=4), KCNJ2 (n=2), KCNE2 (n=2) and CALM2 (n=1). 53,3% of the reports were negative. However, there were some incidental findings: 2 index cases carried P variants in LDLR, 2 carried P variants in PKP2, 2 carried a P variant in MYBPC3 and 1 index case each carried a P variant in DES, TTN and DSG2. From the 231 inconclusive reports, 37 index cases carried the RF variant in KCNE1 (p.Asp85Asn), 2 carried the RF variant in SCN5A (p.Arg1193Gln) and 50 patients carried hot-VUS in KCNQ1, KCNH2, CACNA1C, SCN5a or RYR2 gene. Conclusions In our large cohort of index cases referred for genetic testing for LQTS, diagnostic yield was around 27% when considering only LP/P variants in LQTS or arrhythmic phenotype related genes. Even by including the inconclusive but potentially relevant genetic results (RF and hot VUS), the diagnostic yield in our cohort reaches 35%. This is lower than expected for LQTS cohort. It should be taken into consideration that our cohort consists of heterogeneous patients referred for LQTS genetic testing, which would probably reflects better the real world patients seen in every day practice.