IntroductionIn Mexico, delays in pediatric cancer diagnosis remain a major barrier to timely care and are partly driven by inefficiencies in referral pathways. This study aimed to evaluate the impact of a direct pathway on referral intervals for patients with suspected childhood cancer treated at a high-specialty hospital in Mexico.MethodsWe conducted a retrospective observational cohort study based on a comprehensive review of medical records of patients referred to a high-specialty hospital in Mexico between 2017 and 2022. Patients' characteristics, along with dates from symptom recognition to diagnosis, were collected. The exposure was the referral pathway: standard versus direct (Golden Code strategy) pathway, which enables access to pediatric oncology through a zero-rejection policy. The primary outcome was the time attributable to oncological referral (TAOR), analyzed as a continuous variable and a dichotomous outcome. Secondary intervals were calculated using standardized definitions. Regression models were used to evaluate factors associated with untimely (>7 days) referral.ResultsA total of 399 patients were included. The direct pathway was associated with a shorter TAOR compared to the standard pathway (median 2.0 vs. 7.0 days; p<0.001). The proportion of timely referrals was substantially higher in the direct pathway (91.3%) than in the standard (50.6%) and reduced the likelihood of an untimely referral (OR = 0.098, 95% CI: 0.055-0.173; p<0.001). No differences were observed in other diagnostic intervals.ConclusionThe direct referral pathway improves the timeliness and consistency of access to pediatric oncology care by reducing referral delays and increasing the proportion of patients evaluated within recommended referral intervals. However, the absence of changes in the secondary intervals, such as time to oncological diagnosis, highlights the need for complementary actions targeting downstream diagnostic processes. Strengthening referral systems represents a feasible and impactful strategy to address delays in pediatric cancer care in middle-income settings. In Mexico, many children and adolescents with suspected cancer experience delays before seeing a cancer specialist. These delays can occur for various reasons, including the organization of the health system. When referrals move slowly through several levels of care, diagnosis and treatment may be postponed. This study examined a program called the Golden Code, which is designed to help children with possible cancer access a pediatric cancer specialist more quickly. The program allows doctors to refer patients directly to a specialized hospital, reducing administrative steps and speeding up appointments. Researchers reviewed the medical records of 399 children and adolescents treated between 2017 and 2022. They compared those referred through the Golden Code program with those referred through the usual system. The results showed that children referred through the Golden Code were seen by a cancer specialist much faster. On average, they had their specialist visit within two days, compared to seven days under the standard referral system. The program greatly reduced the chances of a delayed specialist visit. These findings show that improving how patients are referred within the health system can make an important difference in how quickly children with suspected cancer receive expert evaluation. Although Mexico performs better than some countries with fewer resources, further improvements in referral processes and access to care could help ensure children receive timely diagnosis and treatment.
A 13-year-old neutered female domestic shorthair cat was referred for weight loss, polyphagia, polyuria, polydipsia and intermittent vomiting. Blood work demonstrated diabetes mellitus; abdominal ultrasonography revealed a hypoechoic, thickened pancreas with two large fluid-filled cavities within the body and right limb. Cytology of the aspirated fluid indicated suppurative inflammation with bacterial infection, which cultured Pasteurella multocida. Medical management for diabetes mellitus and pancreatic abscessation was initiated. After approximately 4 months of antimicrobial therapy and five percutaneous drainages, clinical signs improved; nevertheless, serial abdominal ultrasonography demonstrated persistent pancreatic abscessation, while repeated cultures and antibiograms documented progressively resistant bacterial infections. The condition culminated in abscess rupture and septic peritonitis, prompting surgical drainage and omentalisation. Histopathological examination of the pancreatic parenchyma revealed severe lymphoplasmacytic pancreatitis with glandular atrophy, while evaluation of the pancreatic tissue associated with the abscess demonstrated a suspected pancreatic exocrine neoplasm, most compatible with a well-differentiated adenocarcinoma. This case highlights the need for earlier consideration of surgical intervention in cases of recurrent pancreatic abscessation and underscores the importance of including concurrent pancreatic neoplasia as a differential diagnosis in chronic, non-resolving presentations.
Scrub typhus has nonspecific symptoms, making it easy to miss or underdiagnose. This retrospective study evaluated targeted next-generation sequencing (tNGS) for the early diagnosis of acute Orientia tsutsugamushi infection in terms of feasibility and application value. This retrospective study included 49 patients with suspected scrub typhus as the case group. Among them, 28 patients with eschar or ulcers were assigned to the clinical diagnosis group. The remaining 21 patients without eschar or ulcers formed the clinically suspected group. Additionally, 48 patients with nonscrub typhus bloodstream infections during the same period were included in the negative control group. Clinical data and tNGS results were collected for all the patients. No significant differences were found between the clinical diagnosis group and the clinically suspected group in sex, age, time from onset to sampling, season of onset, complications, or clinical prognosis (p > 0.05). The sensitivity of tNGS for diagnosing scrub typhus was 91.8% (45/49), and the specificity was 100.0% (48/48). No significant differences were observed between the clinically diagnosed group and the clinically suspected group regarding the positivity rate of O. tsutsugamushi detected by tNGS or the therapeutic response to doxycycline (p > 0.05). Significant changes were observed in the median eosinophil count (EOS), platelet count (PLT), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) before and after doxycycline treatment in the case group (p < 0.001). TNGS demonstrated high sensitivity and specificity for the detection of O. tsutsugamushi. It facilitates the early diagnosis of scrub typhus, particularly in suspected cases without eschars. However, prospective studies are needed for validation.
Predictive biomarkers for symptomatic tuberculosis (TB) progression would transform targeted prevention efforts. Although interferon-gamma release assays (IGRAs), including QuantiFERON® TB-Gold Plus (QFT-Plus), have been studied for this purpose, systematic evaluation of the QFT-Plus TB1 and TB2 Interferon-Gamma (IFNγ) concentrations remains limited, particularly in high-burden TB settings. Baseline TB1 and TB2 IFNγ concentrations from 5246 participants (ages 15-34 years) in TB-endemic regions were analyzed in relation to subsequent TB outcomes over a median of 525 days follow-up (NCT05190146). Participants were categorized as controls (no TB), suspected TB (no microbiological confirmation), or laboratory-confirmed TB, including a subset meeting a stringent case definition (≥2 positive microbiologic tests). Associations between baseline IFNγ concentrations and progression to symptomatic TB were assessed. In the full cohort (IGRA+/- participants), baseline TB2 IFNγ concentrations were significantly higher compared with controls among participants who developed suspected TB (P = .01), laboratory-confirmed TB (P = .01), or met the stringent case definition (P < .0001). In IGRA+ participants, baseline TB2 concentrations were significantly higher than controls in suspected (P = .01) and laboratory-confirmed (P = .02) groups. Associations with baseline TB1 IFNγ concentrations and TB progression were observed for participants meeting the stringent case definition within the full cohort (P = .001). Among stringent definition cases, TB2 concentrations achieved an area under the receiver operating characteristic curve of 0.84, with sensitivity of 80% and specificity of 78%. Quantitative IFNγ concentrations from QFT-Plus, particularly TB2, were associated with progression to symptomatic TB, met or exceeded WHO-recommended sensitivity and specificity thresholds for predictive biomarkers, and may support biomarker-based stratification in TB clinical research.
Timely transfer of patients with suspected LVO remains critical in acute stroke systems. Artificial intelligence (AI)-based imaging tools are increasingly implemented to support triage in non-thrombectomy centres. We assessed whether integrating an AI algorithm within established tele-stroke centres reduces time to transfer decision. We conducted a prospective, multicentre, quasi-experimental study comparing consecutive cohorts in 2 tele-stroke centres referring to a single comprehensive stroke centre, before and after implementation of the Methinks Stroke Suite, an AI algorithm for LVO detection on non-contrast CT (NCCT) and CTA. Consecutive transferred patients with suspected acute ischaemic stroke were included. Remote vascular neurologists retained responsibility for final transfer decisions. Each phase spanned approximately 15 months. The primary outcome was time from arrival at the local centre to emergency medical services activation. Secondary outcomes included workflow intervals, imaging utilisation and algorithm performance. We included 265 patients (136 in the post-implementation cohort; 129 in the pre-implementation cohort). Adjusted median time from arrival to transfer request did not differ (median difference - 2.40 min; 95% CI, -6.16 to 4.48). Post-implementation, time from imaging to transfer request (-7.16 min; 95% CI, -13.02 to -1.85) and arrival to groin puncture (-31.28 min; 95% CI, -60.89 to -13.74) decreased. Computed tomography angiography acquisition at referring centres increased (28%-81%), reducing repeat imaging at the comprehensive centre (79%-42%). Non-contrast CT-based AI prediction yielded a positive predictive value of 66% for endovascular treatment. Artificial intelligence implementation was not associated with a shorter time to transfer decision. Fewer redundant imaging examinations were associated with a shorter time to reperfusion.
Two rescued juvenile cats with unilateral severe shoulder deformities (SDs) suspected to be secondary to septic arthritis were referred for further management. Comprehensive diagnostic evaluations confirmed SD with suspected septic arthritis in both cases. Because of the poor prognosis for preserving shoulder joint function, shoulder arthrodesis was performed to relieve pain and restore forelimb weightbearing ability. At 6 and 8 years postoperatively, both cats exhibited normal motor function in the affected limbs, no signs of lameness and maintained a good quality of life. No evidence of osteomyelitis or implant failure was noted. These findings suggest that arthrodesis may be a viable and effective long-term treatment option for irreparable shoulder joint disorders in cats. Shoulder joint injuries and disorders are less common in cats than in dogs, and only a limited number of reports exist in the small animal orthopaedic literature. In clinical practice, SD in small animals is rarely documented, with few references regarding its aetiology and pathophysiology. This report presents two cases of SD in rescued cats, demonstrating that shoulder arthrodesis can be an effective treatment for irreparable feline shoulder joint disorders. To the best of our knowledge, this is the first report to describe long-term clinical and radiographic outcomes of shoulder arthrodesis in cats with SD. Surgical fusion of the shoulder joint to treat severe shoulder deformity caused by infection in two cats Two young rescued cats were referred for treatment of severe deformities of one shoulder, likely caused by infection in the joint at an early age. Because the shoulder joints could not be repaired, a surgical procedure called shoulder arthrodesis (joint fusion) was performed to reduce pain and allow the cats to use their front legs normally. Both cats recovered well and were able to walk and use their affected limbs without lameness. Long-term follow-up at 6 and 8 years after surgery showed stable implants, successful bone fusion, and no signs of infection, with both cats maintaining a good quality of life. Shoulder joint problems are less common in cats than in dogs, and there are very few reports describing this condition or its treatment in cats. This case report shows that shoulder arthrodesis can be an effective long-term treatment option when the shoulder joint cannot be preserved. To our knowledge, this is the first report to describe long-term clinical and imaging outcomes of this procedure in cats with severe shoulder deformity.
Post-surgical pyoderma gangrenosum (PSPG) is a challenging diagnosis associated with significant morbidity, often misidentified as postoperative infections, leading to inappropriate management. This systematic review aims to elucidate the characteristics, management strategies, and outcomes of PSPG in the context of foot and ankle surgery to improve diagnostic accuracy and patient care. A systematic literature search was conducted across multiple databases, including PubMed, Scopus, and Embase, for cases of PSPG following foot and ankle surgery published up to January 2023. Data on demographics, clinical presentation, management, and outcomes were extracted and analyzed. Ten cases met the inclusion criteria, predominantly females presenting with rapidly worsening and painful postoperative ulcers. A high rate of negative cultures was observed during the patients' treatment period. Dermatology consults initially suspected 83.33% of the cases. Notably, 30% of patients underwent amputation of various parts of the lower extremity, all diagnosed more than 35 days after symptom onset, and were female. The mainstream treatment for PSPG involved systemic immunosuppressants, with corticosteroids being the most common, effectively resolving symptoms in the majority of instances. PSPG should be suspected in patients with unexplained, worsening postoperative wounds. Early recognition and appropriate treatment with immunosuppressants are crucial to prevent severe outcomes. Multidisciplinary management involving dermatologists and surgeons is recommended to optimize patient outcomes. Further research is needed to establish robust diagnostic and management protocols for PSPG in the surgical context.
The accurate and timely diagnosis of inherited retinal diseases (IRDs) represents an unmet clinical need in ophthalmology, as the current pathways rely on resource-intensive phenotyping, multidisciplinary expertise and genetic testing. Here we developed Retina4IRD, an artificial intelligence (AI)-based clinician decision support system (CDSS) that predicts 17 genotype categories from retina images. Retina4IRD uses a Vision Transformer model pretrained with RETFound. We then trained and validated Retina4IRD using multimodal data with color fundus photographs and optical coherence tomography scans from 1,843 genetically confirmed patients (3,376 eyes) across China, South Korea and Poland. The top-5 prediction accuracy was 0.904 (95% confidence interval (CI): 0.896-0.912) and 0.856 (95% CI: 0.850-0.863) for internal and external validation, respectively. We conducted a randomized controlled trial with 300 participants with suspected IRD randomized 1:1 to either Retina4IRD-assisted specialist arm or specialist-only arm. Of these, 295 participants (median age 33 years, 114 (38.6%) females) with available next-generation sequencing reports were included in the final analysis. The primary outcome was met: top-5 genetic accuracy was significantly higher in the Retina4IRD-assisted specialist arm versus the specialist-only arm (88.5% versus 67.3%, P < 0.001). For secondary endpoints, top-1 to top-4 accuracies all favored the Retina4IRD-assisted specialist arm, with top-1 accuracy of 37.8% versus 22.4% and top-4 accuracy of 81.8% versus 53.1%, respectively. Post hoc analyses demonstrated that, with Retina4IRD assistance, clinicians made better management decisions, and the composite downstream management score indicated significantly higher scores relative to the control group (37.7 versus 28.5, P < 0.001). Our study shows that Retina4IRD is a CDSS tool prior to genetic testing and aligns with clinical workflow for patients with suspected IRDs. ClinicalTrials.gov identifier: NCT06839170 .
Pulmonary infections are common and potentially life-threatening in critically ill patients. Conventional microbiological tests (CMTs) often show limited sensitivity, particularly in the setting of prior antimicrobial exposure. Targeted next-generation sequencing (tNGS) has emerged as an alternative approach for broad pathogen detection; however, data describing pathogen spectrum, mixed infection patterns, and diagnostic performance in critically ill populations remain limited. This retrospective study included 217 critically ill patients with suspected pulmonary infection who underwent tNGS testing of respiratory specimens. Baseline clinical characteristics were summarized. The pathogen spectrum and mixed detection patterns identified by tNGS were analyzed, including mixed microbial codetection. Diagnostic performance of tNGS was compared with that of CMTs using clinical diagnosis as the reference standard. Sensitivity, specificity, accuracy, agreement indices, and McNemar's test were applied. tNGS detected at least one microorganism in 208 of 217 patients, yielding a significantly higher overall detection rate than CMTs. A broad spectrum of bacterial, viral, and fungal pathogens was identified, and mixed detections were common, frequently involving organisms from different pathogen categories. Co-occurrence network analysis highlighted recurrent patterns of mixed microbial detection in this cohort. Compared with CMTs, tNGS demonstrated substantially higher sensitivity and overall diagnostic accuracy, whereas conventional methods showed higher specificity. tNGS provides a comprehensive overview of the pathogen spectrum and mixed detection patterns in critically ill patients with suspected pulmonary infection. Compared with CMTs, tNGS offers a markedly higher detection rate and sensitivity. However, careful clinical interpretation remains essential, particularly in the context of frequent mixed microbial detections, to ensure appropriate integration of sequencing results into clinical decision-making.
Ultrasound (US) is currently the primary modality for assessing acute appendicitis in children. However, as rapid abdominal magnetic resonance imaging (MRI) protocols become more readily available, using MRI as a first-line modality in certain patients may decrease the need for additional studies and reduce time to diagnosis. This study evaluates imaging utilization patterns for suspected appendicitis at a large pediatric emergency department and identifies clinical scenarios where MRI may serve as a more efficient first-line imaging modality. We retrospectively analyzed 5856 pediatric and young adult patients who underwent US, MRI, or both for suspected appendicitis (2016-2023), focusing on imaging utilization, demographics, and examination timing. US was used as the primary modality in 86% of cases, with 22% of these patients requiring subsequent MRI. 7% of patients underwent MRI first. Time from imaging order to completion was significantly longer for the US + MRI group (217.72 min) compared to US-only (101.82 min) or MRI-only (120.75 min) (p < 0.001). Age, weight, and female sex correlated with increased US examination duration (p < 0.001), whereas MRI times remained consistent. MRI use increased from day (20.3%) to evening (23.4%) to night (29.5%), while US use declined but remained the dominant modality (p < 0.001). Nearly a quarter of patients undergoing US for appendicitis evaluation ultimately proceed to MRI, resulting in diagnostic delays. MRI may be underutilized as a first-line modality in this subset of patients.
Phenotypic presentations and aetiologies of disorders/differences of sex development (DSD) are variable. While postnatal management is well described, no consensus exists regarding prenatal care, despite increasingly frequent detection. To describe prenatal management practices of isolated ultrasound suspicion of DSD referred to the Multidisciplinary Center for Prenatal Diagnosis (MCPD) of Lyon over a 10-year period. Retrospective study of pregnancies referred to MCPD between January 2013 and December 2022 for isolated ultrasound suspicion of DSD. Foetuses referred for family history risk were not included. DSD were considered isolated when no additional malformation was suspected at referral, except minor cardiac anomalies, renal pelvis or ureteral dilation and intrauterine growth restriction (IUGR). 71 patients were referred for suspected isolated DSD, 57 were confirmed by experts. At birth, 52.3% newborn were preterm and 52.3% had IUGR. Among the 57 prenatally suspicion, 41 children presented a DSD phenotype. SRY testing on maternal blood was performed in 17.5% of cases and invasive examination in 59.6% of cases. Amniotic fluid analyses included steroid profile (76.5%), biochemical analyses for SLO (64.7%) and genetic analyses (100%). Genetic analyses comprised karyotype (100%), CGH array (67.6%), DSD panel (14.7%), targeted gene analysis (35.3%). A molecular diagnosis was obtained in 13 cases, including 5 prenatally. Three fetuses were ultimately diagnosed with severe neurological condition. Prenatal assessment may support counselling and care planning for families expecting a child with DSD. Further prospective studies are necessary to confirm these findings and formulate recommendations for prenatal management of DSD.
To compare the diagnostic efficacy of white light endoscopic (WLE), narrow band imaging (NBI), and iodine staining, both individually and in combination, for the detection of early esophageal cancer (EC) and precancerous lesions. A retrospective analysis was conducted on 55 patients with suspected early EC or precancerous lesions who were treated at Wuxi Second People's Hospital between January 2022 and June 2023. All patients underwent simultaneous endoscopic examination using WLI, NBI, and iodine staining. A total of 63 lesions were identified. Surgical histopathological results and/or follow-up confirmation served as the gold standard. The diagnostic performance (including accuracy, sensitivity, and negative predictive value) of each method individually and in combination was observed and compared. Among the 63 suspected lesions, 5 cases of early EC and 37 cases of precancerous lesions were confirmed by histopathology or follow-up. The combined diagnostic and iodine staining approach demonstrated significantly higher accuracy and sensitivity for early EC compared to WLI or NBI alone (P < 0.05). Agreement with pathological findings was poor for WLI (Kappa = 0.327), fair for NBI (Kappa = 0.476), fair for iodine staining (Kappa = 0.577), and substantial for the combined method (Kappa = 0.715). Among negative lesions, the false positive rate for mucosal staining was lower than that for background coloration. Both endoscopic NBI and iodine staining exhibit relatively high clinical detection rates for early EC and precancerous lesions. Their combined use can further enhance the detection rate of these conditions.
The use of complementary health products (CHPs), including Chinese Proprietary Medicines (CPMs), health supplements, traditional medicines and homeopathic medicines, has become increasingly prevalent in Singapore's multicultural society. While these products are widely used for maintaining health and treating minor ailments and are generally safe, potential adverse effects have been reported. This study analyzes adverse event reports related to CHPs submitted to Singapore Health Sciences Authority (HSA) from 2017 to 2023. AE reports involving CHPs assessed by the Vigilance and Compliance Branch (VCB) of HSA from 2017 to 2023 were collated and analyzed. The analysis included patient demographics, AE details, suspected product information, medical history, laboratory results, concomitant therapies, and reporter's profession. Of the 182,131 AE reports associated with pharmaceutical products and CHPs, 727 reports (0.4%) were associated with CHPs. Health supplements accounted for the highest number of reports (68% of total). "Skin and appendages disorders" were the most commonly reported system organ class, with glucosamine-containing products accounting for the highest number of adverse events. Patients primarily used CHPs for pain relief (33.1%), general health and wellbeing (20.6%), and weight management (8.8%). Products found to contain undeclared illegal substances were most frequently indicated for pain relief. The three most common adulterants were dexamethasone, chlorpheniramine, and prednisolone. While CHPs are generally safe, adulterated products, especially those from dubious sources, pose real health risks. Healthcare professionals and consumers should remain vigilant about potential adulteration and report suspected CHPs related AEs. Even when causality remains unclear, reporting supports timely regulatory actions when concerning patterns emerge. This study examined 727 adverse event reports associated with CHPs between 2017 and 2023, accounting for 0.4% of all reported adverse events. Health supplements were the most frequently reported category, with glucosamine-containing products accounting for the highest number of adverse events, predominantly affecting the skin. Products found to contain undeclared illegal substances were most frequently indicated for pain relief, with dexamethasone, chlorpheniramine, and prednisolone being the most common adulterants found. These findings highlight the need for continued vigilance in the monitoring of CHPs to safeguard public health.
Background Maternal sepsis remains a major cause of maternal morbidity and mortality, particularly in resource-limited settings where early recognition is often delayed. However, conventional sepsis scoring systems have limited applicability in pregnancy because physiological adaptations of gestation can mimic features of sepsis and affect score performance, highlighting the potential role of pregnancy-specific tools, such as the Sepsis in Obstetrics Score (SOS), for risk stratification. Materials and methods This analytical cross-sectional study was conducted at a tertiary care center in Bhopal, India, from January 2022 to January 2023. A total of 450 antenatal women with suspected infection were included. The SOS was calculated at admission using pregnancy-adjusted physiological and laboratory parameters and categorized as low risk (SOS <6) or high risk (SOS ≥6), indicating increased risk of severe sepsis-related adverse outcomes. Associations between clinical variables and elevated SOS were assessed using the chi-square test with odds ratios (OR). Continuous variables were compared using the independent samples t-test. Multivariable logistic regression analysis identified independent predictors of elevated SOS. Results Among the 450 participants, 50 (11.1%) were categorized as high risk (SOS ≥6). Significant predictors of elevated SOS included ≥4 vaginal examinations, premature rupture of membranes (PROM), PROM lasting >24 hours, and abnormal vaginal discharge. Multivariable analysis identified PROM >24 hours (adjusted OR (aOR) 3.48), ≥4 vaginal examinations (aOR 3.05), and abnormal vaginal discharge (aOR 2.21) as independent predictors. Women with elevated SOS scores demonstrated significant physiological derangements. Conclusions The SOS may be useful as a bedside risk-stratification tool among antenatal women with suspected infection. Elevated SOS was primarily associated with modifiable intrapartum and infection-related factors, highlighting potential opportunities for preventive obstetric interventions.
BARD1 germline pathogenic variants (gPV) have been primarily associated with moderate breast cancer risk but their rarity limits accurate risk assessment and tailored follow-up guidelines. Our study evaluates the association between BARD1 gPV and breast cancer while exploring the role of BARD1 in mammary oncogenesis. In this case-control study, 7,309 women with breast cancer and no gPV identified in the French hereditary breast and ovarian cancer (HBOC) gene panel at the Institut Curie were compared to 57,681 female controls from the gnomAD European non-cancer database. Tumors were analyzed for biallelic BARD1 inactivation and homologous recombination deficiency (HRD). A significant association was observed between BARD1 gPV and breast cancer (OR = 5.2, 95% CI [3-8.9], p = 5.9 × 10- 9). Molecular data were obtained and interpretable for seven tumors. Among these, two triple-negative (TN) primary tumors exhibited both biallelic BARD1 inactivation via loss of heterozygosity (LOH) and an HRD phenotype; one metastasis displayed LOH without HRD. All non-TN primary tumors lacked both biallelic inactivation and HRD. We found a strong enrichment of BARD1 gPV among women selected for personal and family history of breast cancer, reinforcing their relevance for genetic testing for suspected hereditary predisposition. Tumor analysis suggests a potential association between biallelic inactivation of BARD1 and the HRD phenotype in TN primary breast tumors, providing new treatment perspectives.
Background: Spinal epidural abscesses (SEA) are rare, occurring 2.5-3 times per 10,000 hospital admissions. While streptococcus species comprise 7% of reported SEAs, Group A Streptococcus (GAS) has been described only once in the medical literature to our knowledge. Case presentation: We present a case of GAS pharyngitis with subsequent paraplegia from a GAS SEA. A 33-year-old female presented to the emergency department (ED) and was initially diagnosed with GAS pharyngitis and a suspected strained lower back. Following treatment with amoxicillin, she returned with worsened back pain, radiculopathy, and leukocytosis, for which she was treated with cyclobenzaprine. On her third presentation, she had new bilateral lower extremity weakness with decreased sensation, bilateral ankle clonus, and hyperreflexia. MRI of the thoracic and lumbar spine revealed a multiloculated SEA at T5-T10 requiring laminectomy and abscess evacuation. Intraoperative cultures grew Streptococcus pyogenes. Despite surgery, medical management, and physical therapy, she remained paraplegic. Conclusions: To our knowledge, this is the first report of SEA preceded by GAS pharyngitis. This case exposes the critical association between a recent infection, progression of back pain, eventual neurologic symptoms, and inflammatory markers that should trigger concern for SEA and early evaluation with MRI.
Mamushi (Gloydius blomhoffii) bite is the most common type of snakebite in Japan. However, clinical information on pediatric patients remains limited. This study aimed to clarify the clinical characteristics of pediatric cases of mamushi envenomation by making comparisons with adult cases. This secondary analysis used data from the OROCHI study, a multicenter prospective observational study conducted at 24 hospitals in Japan, of patients hospitalized for confirmed or suspected mamushi envenomation. The primary outcome was hospital stay. Secondary outcomes included adverse events, pain scores, and the grade of swelling. Patients were classified into pediatric (< 18 years) and adult (≥ 18 years) groups. Of the 106 patients enrolled in the OROCHI study, 99 met the inclusion criteria for this analysis (7 pediatric cases; 92 adult cases). There was no significant difference in median (interquartile range) hospital stay between the pediatric and adult groups (4 days; p = 0.375). Among patients who received antivenom, no adverse reactions were observed in the pediatric group, whereas four adults experienced adverse reactions, including one case of anaphylaxis. The pain scores at antivenom administration were higher in pediatric patients (median 10 vs. 5), but no significant differences were observed after 6 h. The grade of swelling did not differ significantly between the groups at any time point. The clinical course and outcomes of pediatric patients with mamushi envenomation appear similar to those of adult patients. Further accumulation of pediatric cases is warranted to strengthen these findings.
Early referral of patients with suspected sagittal suture synostosis is important as it enables minimally invasive surgery. To encourage early referrals, the authors' craniofacial center has increased its efforts to educate referring healthcare providers. This study evaluated the developments of timely referral and age at referral of patients with sagittal suture synostosis. Nonsyndromic patients born between 2000 and 2020 were included in this cohort study. The type of surgery was mainly based on age at referral: frontobiparietal remodeling was done if the patient was older than 6 months of age, and a minimally invasive procedure was done if the patient was younger. Logistic regression was performed to assess the relationship between the year of birth and the probability of a timely first visit (i.e., before 5.5 months). A total of 698 patients were included, with a median age at first visit of 3.6 months. Of the patients born in 2000, 60% had their first visit before the age of 5.5 months, compared to 77% of those born in 2020. Since 2010, there has been a statistically significant positive association between the year of birth and the probability of having the first visit on time (OR 1.10, 95% CI 1.03-1.18). Overall, pediatricians were the most frequent referrers. The proportion of timely referred patients with nonsyndromic sagittal suture synostosis has increased over the past 20 years, and since 2010, there has been a statistically significant increase in the probability of timely referral, allowing for more patients to be treated with minimally invasive spring-assisted correction. Further efforts are needed to increase timely referrals and raise awareness among parents and healthcare providers.
The adrenal gland plays a pivotal role in the stress response via the hypothalamic-pituitary-adrenal (HPA) axis and the sympatho-adrenomedullary system (SAMS). Congenital adrenal hyperplasia (CAH) results from pathogenic variants in genes encoding adrenal steroidogenic enzymes. The most common form, 21-hydroxylase deficiency, impairs cortisol biosynthesis, leading to compensatory overproduction of adrenocorticotropic hormone (ACTH) and chronic adrenal hyperplasia. A 40-year-old man was referred for incidentally detected bilateral adrenal lesions on abdominal computed tomography (CT). CT revealed marked bilateral adrenal enlargement with clear contours. One month before admission, he had an acute upper respiratory tract infection and recovered after treatment with a cephalosporin. On admission, physical examination showed hyperpigmentation of the nipples region, lips, gums, and buccal mucosa. Superficial lymph nodes were palpable. He reported a history of infertility and suspected precocious puberty. Endocrinology markers demonstrated an elevated ACTH level (180 ng/L; reference range 5.0-78.0 ng/L) with a cortisol level of 174 nmol/L (reference range 133.0-537.0 nmol/L). Luteinizing hormone and follicle-stimulating hormone levels were both low, whereas dehydroepiandrosterone sulfate was elevated. Markedly elevated 17α-hydroxyprogesterone levels and a blunted cortisol response were observed under ACTH-stimulated conditions. Based on the clinical phenotype and biochemical findings, CAH due to 21-hydroxylase deficiency was diagnosed and considered consistent with the simple virilizing form, which was subsequently genetically supported by the CYP21A2 I172N homozygous mutation in exon 4. Remarkably, without any specific treatment, adrenal volume decreased substantially within one month, from 61.06 cm3 to 33.47 cm3, corresponding to an approximately 1.8-fold reduction, although the adrenal glands remained enlarged compared with normal reference values. After excluding adrenal-related tumors, hemorrhage, infections and autoimmune diseases, we postulated that the transient morphological changes reflected stress-induced compensatory hypertrophy and/or hyperplasia of the adrenal cortex following the respiratory infection, aimed at augmenting cortisol production to modulate inflammation and maintain homeostasis. In patients with 21-OHD and residual enzymatic activity, infectious stress may trigger transient enlargement of pre-existing adrenal hyperplasia, potentially as a compensatory response to increased cortisol demand, followed by partial regression after stress resolution.
Plasmodium vivax relapse remains a key barrier to malaria elimination in Latin America. Historically, radical cure relied on multi-day primaquine regimens, often without prior glucose-6-phosphate dehydrogenase (G6PD) testing. In November 2024, WHO issued a recommendation specific to South America for radical cure with primaquine or single-dose tafenoquine after testing G6PD activity. We assessed the operational feasibility of implementing this revised radical cure algorithm, integrating point-of-care quantitative G6PD testing to guide primaquine or tafenoquine selection, under routine care, measured by health-care provider (HCP) compliance. This prospective, observational study in Loreto, Peru (Aug 2022-Dec 2024) evaluated implementation of a revised radical cure algorithm among patients by trained routine HCPs across 14 health facilities. HCP compliance was assessed from the provider (correct algorithm application in ≥80% of patients per HCP role) and patient perspectives (proportion correctly treated per algorithm). Safety endpoints included acute haemolytic anaemia (AHA) and other serious adverse events. Among 187 HCPs and 987 patients, HCP compliance was 96.6% (172/178) from the provider perspective and 98.7% (974/987) from the patient perspective, with similar results across urban/periurban and remote/rural facilities. Incorrect treatments (1.3%; 13/987) were mostly due to operational lapses in treatment sequencing and eligibility among G6PD-normal individuals. Ten patients (1.1%; 10/916) developed symptoms suggestive of AHA; one met suspected AHA criteria, unconfirmed. Eight patients (0.8%; 8/986) experienced serious adverse events attributable to severe malaria; all recovered. HCPs across participating facilities achieved high compliance with the revised radical cure algorithm from both perspectives and consistently across urban/periurban and remote/rural settings. Incorrect treatments were infrequent and no AHA was confirmed. These findings demonstrate that HCP at the participating facilities can successfully implement the revised radical cure algorithm, contributing to the operational evidence base informing its scale-up in Peru and the Americas. Unitaid (Grant number 2021-43-VIV). La recaída por Plasmodium vivax sigue siendo un obstáculo clave para la eliminación de la malaria en América Latina. Históricamente, la cura radical se basaba en regímenes de primaquina de varios días, a menudo sin pruebas previas de glucosa-6-fosfato deshidrogenasa (G6PD). En noviembre de 2024, la OMS emitió una recomendación específica para Sudamérica sobre la cura radical con primaquina o tafenoquina en dosis única, tras realizar pruebas de actividad de G6PD. Evaluamos la viabilidad operativa de implementar este algoritmo revisado de cura radical, integrando pruebas cuantitativas de G6PD en el punto de atención para guiar la selección de primaquina o tafenoquina, en el contexto de la atención rutinaria medido mediante el cumplimiento del personal de salud. Este estudio prospectivo y observacional realizado en Loreto, Perú (agosto de 2022 a diciembre de 2024) evaluó la implementación de un algoritmo revisado de cura radical en pacientes atendidos por personal de salud capacitado en 14 establecimientos de salud. El cumplimiento del algoritmo por parte del personal sanitario se evaluó desde la perspectiva del proveedor (aplicación correcta del algoritmo en ≥80 % de los pacientes por rol del profesional) y del paciente (proporción de pacientes tratados correctamente según el algoritmo). Los criterios de valoración de seguridad incluyeron anemia hemolítica aguda (AHA) y otros eventos adversos graves. Entre 187 profesionales sanitarios y 987 pacientes, el cumplimiento del protocolo fue del 96.6 % (172/178) desde la perspectiva del proveedor y del 98.7 % (974/987) desde la perspectiva del paciente, con resultados similares en establecimientos de salud urbanos/periurbanos y rurales/remotos. Los tratamientos incorrectos (1.3 %; 13/987) se debieron principalmente a fallos operativos en la secuenciación del tratamiento y a la elegibilidad de los pacientes con niveles normales de G6PD. Diez pacientes (1.1 %; 10/916) desarrollaron síntomas sugestivos de AHA; uno cumplió los criterios de sospecha de AHA, sin confirmación. Ocho pacientes (0.8 %; 8/986) experimentaron eventos adversos graves atribuibles a malaria severa; todos se recuperaron. Los profesionales de la salud de los establecimientos participantes lograron un alto grado de cumplimiento con el algoritmo revisado de cura radical, desde ambas perspectivas y de manera consistente en entornos urbanos/periurbanos y rurales/remotos. Los tratamientos incorrectos fueron poco frecuentes y no se confirmó ningún caso de AHA. Estos hallazgos demuestran que el personal de salud en los establecimientos de salud participantes puede implementar con éxito el algoritmo revisado de cura radical, contribuyendo a la base de evidencia operacional que respalda su ampliación en Perú y las Américas. Unitaid (Número de subvención 2021-43-VIV).