Scrub typhus, a zoonotic bacterial infection caused by the arthropod-borne, Gram-negative, obligate intracellular bacillus Orientia tsutsugamushi and transmitted by larval chiggers, is an underdiagnosed cause of acute undifferentiated febrile illness. Its clinical spectrum ranges from a self-limited denguelike illness to rapidly progressive multiorgan dysfunction driven by smallvessel vasculitis, including pneumonitis, acute kidney injury, hepatitis, encephalitis and circulatory shock. Early recognition is frequently missed because the characteristic eschar may be absent or easily overlooked in concealed or pigmented skin sites, and definitive diagnostics such as polymerase chain reaction (PCR) or indirect immunofluorescence assay (IFA) are often unavailable in resource-limited settings. Occupational and environmental exposures, particularly work in oil palm or rubber plantations and contact with forest- estate ecozones, remain key epidemiological clues that may be under-elicited in routine clinical practice. We report a case series of four patients with confirmed scrub typhus presenting to a hospital in Kluang district, Johor, Malaysia. All patients had acute fever and non-specific viral-like symptoms, including malaise, chills, headache and myalgia. Thrombocytopenia and acute kidney injury occurred in 50%, while 75% demonstrated transaminitis. Eschars were identified in all patients following comprehensive dermatological examination. Diagnosis was confirmed by PCR for O. tsutsugamushi DNA, a fourfold rise in IFA titres, or a single high-titre IgM or IgG in a compatible clinical syndrome. Three patients (75%) had clear domiciliary or occupational risk factors, including oil palm work or residence near secondary scrubland. One patient developed organ-threatening complications with acute kidney injury and severe hepatitis, illustrating the vasculitic end-organ involvement of severe scrub typhus. All patients achieved clinical defervescence and symptomatic improvement within 24-48 hours of doxycycline initiation, consistent with the characteristic brisk antimicrobial response. This series underscores the need for a low threshold of clinical suspicion and early empiric rickettsial coverage in undifferentiated febrile illness with relevant exposure in rural Malaysia and highlights the need for larger multicentre studies to define predictors of severity, guide triage and inform prevention in high-risk land-use settings.
Takayasu arteritis is a chronic large-vessel vasculitis that predominantly affects young women and may lead to severe vascular complications. This case series is noteworthy because it describes Takayasu arteritis revealed by severe cardiovascular and neurovascular complications, including ischemic stroke and advanced heart failure, in young women without traditional cardiovascular risk factors. We report three cases of Takayasu arteritis observed at Ibn Rochd University Hospital in Casablanca in 2024. The median age was 38 years. Two patients presented with ischemic stroke, while one presented with advanced heart failure. Clinical examination revealed upper limb claudication, dyspnea on exertion, decreased or absent radial pulses, carotid bruits, and significant blood pressure asymmetry between upper limbs. Laboratory investigations showed an inflammatory syndrome with elevated C-reactive protein and erythrocyte sedimentation rate, as well as inflammatory anemia. The diagnosis was confirmed by multimodal non-invasive vascular imaging, including Doppler ultrasound, computed tomography (CT) angiography, magnetic resonance (MR) angiography, and positron emission tomography (PET) scan, fulfilling the 2022 American College of Rheumatology classification criteria. All patients received high-dose corticosteroid therapy (1 mg/kg/day) followed by progressive tapering. Standard treatment for heart failure was initiated when indicated, and anticoagulation or antiplatelet therapy was prescribed according to the presence of embolic events. Clinical and biological improvement was observed in all patients, with partial neurological recovery and a significant reduction of inflammatory markers. Takayasu arteritis may present with highly polymorphic clinical presentations, including severe cardiovascular and neurovascular complications as initial manifestations in young women without traditional risk factors. Early recognition through multimodal non-invasive vascular imaging is essential to establish the diagnosis promptly and initiate appropriate treatment, thereby reducing the risk of irreversible complications.
Antipsychotics are commonly recommended for the treatment of delirium; however, alternative options are warranted due to the limitations of oral and injectable formulations. The blonanserin (BNS) transdermal patch may improve treatment adherence; however, evidence regarding its efficacy in managing delirium remains limited. This retrospective case series describes 51 cases of delirium managed with BNS patches at Kyoto University Hospital between January 2020 and June 2022. The effectiveness of the BNS patch for delirium, the rationale for its selection, and the associated adverse events were retrospectively evaluated using electronic medical records. Delirium was diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders, 5th edition criteria by physicians from the consultation-liaison or palliative care teams, and the symptoms were regularly monitored. Effectiveness was assessed based on non-standardized clinical judgment documented in the medical records. Hyperactive and mixed delirium were observed in 41.2% and 56.9% of patients, respectively. Overall, the therapeutic response rate across all patients was 84.3%. The main reasons for the selection of BNS patches were difficulty or inability to take oral medications (60.8%). Adverse events occurred in 29.4% of patients; all resolved after discontinuation of the BNS patch, and no serious or irreversible reactions were observed. These findings indicate that the BNS patch has potential as an effective treatment option for delirium, particularly in patients with challenges in the administration of medication. However, given the retrospective and exploratory nature of this study, the findings should be interpreted with caution.
Chronic kidney disease (CKD) in children poses unique challenges, especially in resource-poor developing countries, with limited facilities for renal replacement therapy (RRT). We present three cases of children with end-stage renal disease from Sri Lanka in whom traditional access has been exhausted secondary to sepsis and thrombosis. Three patients were not candidates for peritoneal dialysis, and several attempts for tunnelled and non-tunnelled catheters limited the ability to continue RRT until the donor work-up for transplantation was completed. Therefore, surgical placement of a vascular catheter (vascath) to enter the inferior vena cava (IVC) directly was performed under general anaesthesia. Patient 1, a nine-year-old boy, successfully maintained dialysis through the IVC catheter until transplantation. Patient 2, a fourteen-year-old boy with extensive thrombosis, underwent successful cannulation with good outcomes at 4 months' follow-up. Patient 3, a twelve-year-old girl post-nephrectomy, initially dialysed successfully but later died due to cardiac failure unrelated to the access site. This procedure provided effective haemodialysis access, mitigating severe volume overload and hyperkalaemia. They also tolerated subsequent dialysis sessions well. This case series highlights the critical role of unconventional dialysis access methods in resource-constrained settings, where advanced interventional radiology options may be unavailable. While IVC cannulation for haemodialysis is more commonly described in adults, these are the first reported cases of vascath insertion into the IVC in paediatric patients. Additionally, these findings underscore the importance of innovative strategies to manage paediatric CKD in low-resource settings, pending definitive renal transplantation.
Despite the use of narrow-band imaging, comprehensive endoscopic evaluation of the laryngopharynx in the endoscopy suite remains challenging because of its complex anatomical structure, limited working space, and reactions such as gagging and coughing. Consequently, minute synchronous neoplasms may occasionally be overlooked during the initial endoscopic assessment. We hypothesized that argon-plasma coagulation (APC) could serve as a minimally invasive treatment for minute synchronous neoplasms of the head and neck detected during endoscopic laryngopharyngeal surgery combined with endoscopic submucosal dissection (ELPS/ESD) for primary lesions. We report three cases of pharyngeal cancer treated with ELPS/ESD under general anesthesia: an 82-year-old man, a 73-year-old man, and a 40-year-old woman. During intraoperative endoscopic observation, 9 minute lesions measuring 3-7 mm that had not been detected in the endoscopy suite were identified in 3 patients. These lesions were immediately treated with APC, a non-contact technique that uses ionized argon gas to coagulate abnormal tissue. In Cases 1, 2, and 3, the lengths of hospital stay were 10, 11, and 6 days, respectively, and the follow-up periods were 9 months, 6 months, and 6 months, respectively. Within this limited follow-up period, no post-procedural bleeding, post-procedural hoarseness, or post-procedural swallowing dysfunction was observed. Based on this small case series with limited follow-up, intraoperative APC may be a feasible adjunctive approach for the ablation of minute synchronous lesions detected during ELPS/ESD for pharyngeal cancer.
Splenic artery aneurysm (SAA) rupture is a deceptive cause of sudden unexpected death presenting significant medicolegal challenges. This retrospective case series and comprehensive literature review analyzes the clinicopathological features of six nontraumatic fatal SAA ruptures. Clinical presentations were predominantly nonspecific, resulting in diagnostic delays and medicolegal inquiries in two cases. A size-rupture paradox was observed, as fatal hemorrhage occurred across a wide diameter spectrum (3-12 cm), proving that small aneurysms also carry lethal potential. The literature review elucidates the multifactorial etiopathogenesis of SAA, encompassing genetic, hormonal, hemodynamic, and inflammatory factors. Furthermore, the clinical trajectory of delayed fatality is explained by the double-rupture phenomenon, which creates a deceptive lucid interval. Histochemical evaluation utilizing Elastic Verhoeff-Van Gieson (EVG) staining was pivotal, demonstrating severe internal elastic lamina loss to confirm spontaneous degenerative rupture and exclude trauma. Consequently, meticulous celiac trunk dissection and routine EVG histochemistry must be integrated into forensic autopsy protocols evaluating unexplained hemoperitoneum to accurately determine the cause of death and address liability disputes.
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Pneumoperitoneum is most commonly associated with gastrointestinal perforation and often prompts emergent surgical exploration; however, gynecologic sources such as vaginal cuff dehiscence (VCD) can rarely be the cause. We present two unusual cases of pneumoperitoneum secondary to VCD following remote hysterectomy, each with distinct presentations and operative findings. The first case involves a 38-year-old woman with prior Roux-en-Y gastric bypass and hysterectomy who presented with acute-on-chronic abdominal pain and imaging evidence of free intraperitoneal air. Diagnostic laparoscopy and intraoperative endoscopy ruled out gastrointestinal perforation, and subsequent exploration revealed complete VCD with a localized abscess and adherent small bowel requiring resection and open cuff repair reinforced with an omental patch. The second case involves an 83-year-old woman with a history of hysterectomy and planned vaginal prolapse repair who presented with suprapubic pain and vaginal bulging. Imaging revealed a small bowel herniation through the vaginal vault, and diagnostic laparoscopy confirmed complete cuff dehiscence, which was successfully repaired laparoscopically using barbed absorbable sutures. Both patients recovered uneventfully. VCD remains a rare but potentially serious postoperative complication, with a presentation as pneumoperitoneum being exceptionally uncommon. Awareness of this entity is critical to prevent unnecessary bowel resections when bowel viability is preserved and to guide timely, multidisciplinary management tailored to intraoperative findings.
Mission control, we need a read! Michael Pohlen, MD, joins cohosts Lindsey Negrete, MD, and Amy Maduram, MD, to discuss his incredible journey into space medicine, including engagement with the team leading the first radiograph obtained in space, medical conditions occurring during weightlessness, and the commercial shift into space research.
ObjectiveThe objective was to evaluate the safety, pharmacokinetics and efficacy of an alternative deltoid site for CAR-LA.DesignThis is a prospective cohort of people living with HIV (PLWHIV) switching for intramuscular long acting cabotegravir and rilpivirine (CAR-LA).MethodsClinical and biological data were collected at baseline, month 1 (M1), month 3 (M3), and every three months thereafter, when available.ResultsA total of 15 patients were enrolled between August 2022 and October 2024. Of these, 11 were transgender women, 1 cisgender woman, and 3 cisgender males. The median duration of plasma HIV-1-RNA (pVL) <50 copies/mL before switching to CAR-LA was 42 months. The main criterion for selecting PLWHIV was the presence of injected silicone in the gluteal region (12 out of 15 cases). Median duration of CAR-LA was 13 months. All patients maintained a pVL<50 copies/mL at M1 and M3. No virological failure was observed in the 13 patients who were followed up to M12. One PLWHIV discontinued deltoid injections due to low plasma concentrations at M2, while another discontinued due to non-adherence which led to cabotegravir resistance at M13. Three PLWHIV reported moderate pain at the injection site, with one discontinuing treatment at M12. All CAB and RPV plasma concentrations measured after deltoid CAR-LA were comparable with those obtained following gluteal CAR-LA phase 3 studies.ConclusionDeltoïd CAR-LA seems to be a reliable and well-tolerated alternative for PLWHIV with contraindications for gluteal injections.
[This retracts the article DOI: 10.3389/fmed.2025.1591793.].
Artificial intelligence (AI) presents unique opportunities and challenges in medical education. In this video article, Marc Triola, MD, Director of the Institute for Innovations in Medical Education and Senior Associate Dean for Medical Education at the NYU Grossman School of Medicine, joins host Ali Tejani, MD, to discuss the intentional and ethical integration of AI in medical education, strategies for ensuring that AI literacy is available to all students, and approaches for making AI education sustainable to weather rapid change.
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Despite concerns regarding its validity, the two-alternative forced-choice heartbeat detection task (2AFC-HDT) is a frequently used measure of cardiac interoceptive accuracy. In this task, participants must decide whether a series of tones occur synchronously with their heartbeats. One series of tones is predefined by the researcher as synchronous with heartbeats, and one series is predefined as asynchronous. The 2AFC-HDT may result in individuals judged to be not interoceptive when they are, either if participants perceive their heartbeats as occurring synchronously with tones predefined as asynchronous rather than synchronous with their heartbeats, or if they do not perceive either set of tones as synchronous. Currently, there is little data on the proportion of participants this may affect. We addressed this using data from the Phase Adjustment Task (PAT) - a measure of cardiac interoceptive accuracy that determines if, and when in the cardiac cycle, a participant can perceive their heartbeat. The timing of heartbeat perception in 43 interoceptive participants was compared to the timing of synchronous and asynchronous tones used in the 2AFC-HDT, assuming temporal precision of 50, 100, and 150 ms. Results suggest that between 53.5%-97.7% of delay-based interoceptive individuals perceive heartbeats at a delay that does not correspond to the typical asynchronous or synchronous delays used to present tones on the 2AFC-HDT. These issues suggest that the 2AFC-HDT (or other measures that make assumptions about perceived timing of heartbeats) should not be used to measure cardiac interoceptive accuracy, or cardiac interoceptive insight (also known as awareness or metacognition).
To quantitatively describe viscoelastic properties, we characterized the tensile stress relaxation of human ocular tissues using a Prony series model. Specimens from eight pairs of postmortem human eyes were dissected from six regions: the anterior, equatorial, posterior, and peripapillary sclera; the optic nerve (ON); and the optic nerve sheath (ONS). Each specimen underwent uniaxial tensile loading under controlled physiological conditions at strain levels ranging from 4% to 6% to identify the optimal strain range within which the tissues exhibit linear viscoelastic behavior. Stress relaxation curves were fitted to a generalized Maxwell model using a Prony series to determine tissue-specific relaxation time constants and relative moduli. All tissues exhibited linear viscoelastic behavior within 5% strain. The anterior sclera showed the greatest stress level, with 12.6 MPa instantaneous modulus and 8.8 MPa equilibrium modulus, whereas the ON exhibited the fastest stress decay and lowest stiffness, with moduli of 3.5 MPa and 1.1 MPa, respectively. The ON had the longest long-term relaxation time of 460 ± 77 seconds, and the ONS had the shortest time at 60 ± 5 seconds. Prony series parameters successfully captured the relaxation profiles across all tissues. This study supports the use of Prony-based models for numerical simulation to describe the region-specific viscoelasticity of ocular tissues. These findings provide foundational data for future investigations into ocular biomechanics, particularly under dynamic or pathologic loading.
A series of eight phenanthrene-based phosphorus heterocycles were prepared to evaluate the effect of phosphorus-center modification on the optical and electrochemical properties of π-conjugated systems. A versatile synthetic route provided access to λ3-, λ4-, and λ5-phosphorus derivatives, including phosphinine, phosphine oxide, sulfide, selenide, phosphinic acid, amide, and phosphonium species. The resulting compounds were investigated using DFT calculations in combination with absorption and emission spectroscopy as well as cyclic voltammetry (CV) and differential pulse voltammetry (DPV). The data show that phosphinic acid derivatives exhibit only minor changes in optical and redox properties, whereas chalcogen exchange (O, S, and Se) has a more pronounced effect on the optical behavior. All compounds display irreversible oxidation waves above 0 V. Comparison with carbo and aza analogues revealed that the incorporation of phosphorus into the phenanthrene scaffold leads to a bathochromic shift in both absorption and emission. In contrast, the first reduction potentials (Ered1) remain comparable across the series. Overall, these results provide a systematic overview of the influence of the phosphorus-center modification on the electronic properties of phenanthrene-based systems.
To report the clinical outcomes, return to sport (RTS) and psychological readiness of patients who underwent arthroscopic Bankart repair with knotless all-suture anchors with a minimum follow-up of 2 years. In this retrospective case series, consecutive patients who underwent primary arthroscopic Bankart repair using knotless all-suture anchors between 08/2019 and 07/2022 were included. Patient-reported outcomes were assessed using the Western Ontario Shoulder Instability Index (WOSI), American Shoulder and Elbow Surgeons (ASES) score, Disabilities of the Arm, Shoulder and Hand questionnaire (DASH), Shoulder Instability-Return to Sport after Injury (SI-RSI) scale, subjective shoulder value (SSV), and the visual analogue scale (VAS) for pain. Patient satisfaction, RTS, return to preinjury level of sport, instability recurrence and revisions were recorded. Receiver operating characteristic (ROC) curve was calculated to assess the discriminative performance of the SI-RSI scale, and the Youden's index was employed to determine the optimal cutoff for prediction of return to preoperative level of sports. Of 57 patients eligible for inclusion, 46 patients (11.1% female, 28.7 ± 6.8 years at surgery) were available at a follow-up of 2.9 [2.3-3.4] years. Three patients (6.5%) reported a redislocation, one patient (2.2%) underwent a revision and was excluded from analysis. At final follow-up, an ASES score of 98 (92-100), a DASH score of 2.5 (0-6.7), a WOSI of 11 (3.3-18), an SSV of 93 (85-97) along with low levels of pain were reported. A total of 43 (97.7%) of patients reporting preoperative activity (n = 44) achieved RTS, with 20 patients (45.5%) who had returned to preoperative level of sports. Patients achieving return to preoperative level of sports had a significantly higher SI-RSI scale (89 [83-94]) than those who did not (61 [50-81], p < 0.001). The SI-RSI showed high discriminative performance for return to preoperative level of sports (area under ROC curve: 0.84 [95%CI 0.73-0.97]) with an optimal cutoff of 80 (Youden's index: 0.597). At short-term follow-up, Bankart repair using knotless all-suture anchors demonstrated favorable patient-reported outcomes and low redislocation rates. Patients who did not return to their preinjury level of sport exhibited significantly lower psychological readiness. The SI-RSI exhibited high discriminative performance in predicting return to preoperative level of sports, with an optimal cutoff value of 80. IV - Retrospective case series.
Radially conjugated macrocyclic molecules offer a unique approach to tuning frontier orbital energies by manipulating ring geometry and donor-acceptor (D-A) interactions. Here, we present a systematic DFT study of the electronic structure and metal-molecule energy-level alignment for a series of macrocyclic molecules and their linear counterparts, which include thiophene, diketopyrrolopyrrole (DPP), benzodithiophene (BDT), dithienobenzodithiophene (DTBDT), and benzothiazole (BT) units. Our calculations indicate that macrocyclization induces a system-specific change in the HOMO-LUMO energy gap, with the direction and magnitude depending on the balance between ring strain and D-A coupling strength for each molecule. Among the studied systems, [DTBDT-DPP]3 has the smallest HOMO-LUMO gap, decreasing from 1.13 eV in the isolated macrocycle to 1.44 eV in the Au18 junction model due to electrode-induced orbital hybridization. Its HOMO at -5.31 eV aligns most closely with the Au18 Fermi level, resulting in a hole injection barrier. (Φ h) of approximately 0.01-0.21 eV, making it the most promising candidate for hole injection in this series. These results establish quantitative structure-property relationships across five D-A macrocyclic architectures and offer a computational foundation for the rational design of macrocycle-based organic semiconductors.
Aiming to develop a high-throughput fluorimetric assay for the activity CYP1A2, we introduced 6-Methoxy-2-naphthoic acid (MONA) as a new fluorogenic substrate for this important metabolizer of antidepressants and psychotropic drugs in human liver. We demonstrated that oxidative demethylation of MONA by liver microsomes results in a red shift and a substantial increase in fluorescence. This effect, which is exceptionally well pronounced at alkaline pH, allowed us to develop a sensitive and robust high-throughput assay of MONA metabolism. Probing the activity of 15 individual recombinant human P450 enzymes, we found that only two P450 species exhibited activity in MONA demethylation: CYP1A2 ( k cat =11.9±2.2 min -1 , K M =578±106 µM) and CYP2A6 ( k cat =0.48±0.07 min -1 , K M =54±15 µM). Since the K M values of the two enzymes are well resolved and the turnover rate observed with CYP2A6 is much lower than that of CYP1A2, this new fluorogenic substrate is useful as a specific probe for CYP1A2 activity in HLM. Importantly, MONA is not metabolized by CYP1A1 and CYP2C19, which distinguishes it from all known CYP1A2 fluorogenic substrates. We then used MONA to investigate the effects of chronic alcohol exposure on CYP1A2 activity using a series of 23 proteomically characterized individual HLM preparations from donors with various levels of alcohol consumption. The substrate saturation profiles (SSP) acquired with these preparations were subjected to global kinetic analysis by approximating them with combinations of two Michaelis-Menten equations with globally optimized K M values of 11 and 553 µM. The amplitudes ( V max values) of both components showed a pronounced increase with increasing alcohol exposure of the liver donors. The V max of the minor high-affinity component was best correlated with the abundance of alcohol-inducible CYP2E1 enzyme. The correlation was further improved by combining it with the abundances of CYP2A6 and CPR. This finding suggests that this minor component reflects the activity of CYP2A6 in the complex with alcohol-inducible CYP2E1 protein. In contrast, the V max of the predominant CYP1A2-catalyzed low-affinity component revealed a pronounced correlation with the abundances of CYP1A2 and NADPH cytochrome P450 reductase (CPR). These results suggest a considerable increase in the rate of metabolism of drug substrates of CYP1A2 by chronic alcohol exposure that takes place despite an alcohol-induced decrease in CYP1A2 expression.
The use of plastic waste as a filler in concrete, particularly in paving block production, represents an approach aligned with circular economy principles. While previous studies have focused on mechanical properties, the effect of such materials on slip risk remains insufficiently investigated, especially for pedestrian applications. This study evaluates the influence of the volumetric content of recycled plastic waste from electrical cable insulation on slip resistance of concrete paving blocks. A series of specimens was prepared with 0-45% replacement of natural aggregate by granulated cable insulation (GCI). Slip resistance was measured using the British Pendulum Tester and expressed as Skid Resistance Value (SRV) after statistical processing. Two sliders were used, Mounted Shoe 55 and Mounted Shoe 96, corresponding to road and pedestrian conditions. The results show that increasing GCI content reduces mass by approximately 9.6 g per 1% GCI, reaching a reduction of about 20% at 50% GCI. For polished surfaces, SRV increased up to 77 (MS55) and 75 (MS96) at 40-45% GCI. For ground surfaces, optimal performance was observed at 10% GCI, while higher contents reduced SRV and caused mechanical degradation above 30-35% GCI. The results indicate that optimized GCI content can improve slip resistance while reducing material weight.