bluuebunny/crossref_metadata_2025 huggingface dataset:
Exogenous Sequences in Tumors and Immune Cells (Exotic): A Tool for Estimating the Microbe Abundances in Tumor RNA-seq Data
Authors: Hoyd Rebecca , Wheeler Caroline E. , Liu YunZhou , Jagjit Singh Malvenderjit S. , Muniak Mitchell , Jin Ning , Denko Nicholas C. , Carbone David P. , Mo Xiaokui , Spakowicz Daniel J.
Published: October 2023

The microbiome affects cancer, from carcinogenesis to response to treatments. New evidence suggests that microbes are also present in many tumors, though the scope of how they affect tumor biology and clinical outcomes is in its early stages. A broad survey of tumor microbiome samples across several independent datasets is needed to identify robust correlations for follow-up testing. We created a tool called {exotic} for “exogenous sequences in tumors and immune cells” to carefully identify the tumor microbiome within RNA sequencing (RNA-seq) datasets. We applied it to samples collected through the Oncology Research Information Exchange Network (ORIEN) and The Cancer Genome Atlas. We showed how the processing removes contaminants and batch effects to yield microbe abundances consistent with non–high-throughput sequencing–based approaches and DNA-amplicon–based measurements of a subset of the same tumors. We sought to establish clinical relevance by correlating the microbe abundances with various clinical and tumor measurements, such as age and tumor hypoxia. This process leveraged the two datasets and raised up only the concordant (significant and in the same direction) associations. We observed associations with survival and clinical variables that are cancer specific and relatively few associations with immune composition. Finally, we explored potential mechanisms by which microbes and tumors may interact using a network-based approach. Alistipes, a common gut commensal, showed the highest network degree centrality and was associated with genes related to metabolism and inflammation. The {exotic} tool can support the discovery of microbes in tumors in a way that leverages the many existing and growing RNA-seq datasets.

Significance:

The intrinsic tumor microbiome holds great potential for its ability to predict various aspects of cancer biology and as a target for rational manipulation. Here, we describe a tool to quantify microbes from within tumor RNA-seq and apply it to two independent datasets. We show new associations with clinical variables that justify biomarker uses and more experimentation into the mechanisms by which tumor microbiomes affect cancer outcomes.
Left Superior Homonymous Quadrantanopia due to Giant Virchow-Robin Space
Authors: Lim Michelle , Micieli Jonathan A.
Published: October 2023

A 51-year-old man was referred by his optometrist for an incidental finding of a visual field defect. Humphrey 24-2 SITA-Fast visual field testing revealed a left superior homonymous quadrantanopia, and magnetic resonance imaging of the brain showed a 2.0 × 0.5-cm oblong-shaped cerebrospinal fluid space posterior to the right basal ganglia. This space coursed close to the lateral geniculate body and was thought to represent a giant perivascular (Virchow-Robin) space. This case demonstrates that patients with a visual field defect without other neurological symptoms could be a result of an enlarged Virchow-Robin space along the visual pathway.
Favorable Outcome with Intravenous Immunoglobulin Therapy in Late-Onset Anti-mGluR1 Encephalitis: A Case Report and Literature Review
Authors: Sakashita Kento , Nishida Katsuya , Takenaka Yu , Yokota Ichiro , Yamasaki Hiroshi , Nishimoto Keisuke , Kawamoto Kunihiko , Mitani Maki , Funakawa Itaru , Yoshikura Nobuaki , Kimura Akio , Shimohata Takayoshi , Futamura Naonobu
Published: October 2023

Anti-metabotropic glutamate receptor 1 (mGluR1) encephalitis is a rare autoimmune disorder manifesting with cerebellar syndrome. Patients with mGluR1 encephalitis have been treated with immunomodulatory therapies; however, little is known about the efficacy of this therapy. A 58-year-old Japanese woman presented with dizziness when walking and standing up. Symptoms persisted and the patient gradually deteriorated. The neurological examination revealed a broad-based gait, horizontal and slightly gaze-evoked nystagmus, noticeable head titubation, and truncal ataxia without limb ataxia. Magnetic resonance imaging was normal. The 123I-isopropyl-iodoamphetamine single-photon emission-computed tomography scans showed normal cerebellar perfusion. Based on a positive antibody test for anti-mGluR1, the patient was diagnosed with anti-mGluR1 encephalitis. She was treated with intravenous methylprednisolone and intravenous immunoglobulin (IVIg). Symptoms gradually improved over 1 month and almost disappeared after additional IVIg therapy. Anti-mGluR1 encephalitis is a rare disease, and effective treatment is unclear. In this case, a favorable outcome was obtained with immunomodulatory therapy, even though the neurological disability of the disease course is worse. We emphasize the importance of early diagnosis and therapeutic intervention, suspecting the disease on the basis of its characteristic symptoms.
Presumed Melanocytoma-Associated Choroidal Neovascular Membrane with Hemorrhage Successfully Treated with Intravitreal Aflibercept Injections
Authors: Yu Austin S. , Sugarman Jordan A. , Weiss Stephanie J.
Published: October 2023

A patient presented with melanocytoma and associated choroidal neovascular membrane with hemorrhage involving the macula. The patient was treated with monthly aflibercept (Eylea) injections with significant improvement of best corrected visual acuity. In this report, we explore the development of a choroidal neovascular membrane (CNVM) formation in a patient with melanocytoma and the effect of intravitreal aflibercept (Eylea) on disease course. Case report study used patient data obtained from examination and imaging. The patient was treated with monthly intravitreal aflibercept injections leading to complete resolution of CNVM and hemorrhage, with significant improvement of best corrected visual acuity. Awareness and proper monitoring for the sequelae of melanocytoma are important for early detection and prevention of visually threatening outcomes. In cases of melanocytoma-associated CNVM formation with large subretinal hemorrhage, intravitreal aflibercept can be an effective tool for inducing CNVM regression and allowing improvement of visual acuity.
Possible Spontaneous Extrusion of a Traumatic Deeply Embedded Intracorneal Foreign Body: A Case Report
Authors: AlHazzani Abeer A. , Fatani Dalal R. , Kalantan Hatem
Published: October 2023

Traumatic intracorneal foreign bodies are very common and account for 30.8% of all ocular injuries. Deeply embedded intracorneal foreign bodies have been documented in association with good final visual outcome when managed effectively. We report herein, an unusual case of possible spontaneously extruded deeply embedded intracorneal foreign body 5 weeks after sustaining a trauma to his right eye. Whether the foreign body was truly spontaneously extruded or absorbed by corneal tissue is unknown.
Monitoring Delayed Toxoplasmosis-Related Branch Retinal Artery Occlusion Using Widefield en face Optical Coherence Tomography and Multimodal Imaging
Authors: Iyer Prashanth , Ashkenazy Noy , Liu Jeremy , Laura Diana , Marquez Marilyn Ann , Albini Thomas A.
Published: October 2023

Ocular toxoplasmosis has a known, rare association with acute retinal artery occlusion (RAO). We describe a 21-year-old male who presented with acute focal toxoplasmosis chorioretinitis in the right eye treated with intravitreal clindamycin, intravitreal dexamethasone, and adjunct oral therapy for vision-threatening retinitis with subsequent quiescence. Nine months from his initial presentation, the patient presented with a branch RAO adjacent to an inactive retinal scar in the right eye. Widefield en face structural swept-source optical coherence tomography (SS-OCT) centered on the middle retina showed paracentral acute middle maculopathy (PAMM) in an arteriolar distribution. The patient was started on 81 mg of aspirin daily. Six months later, the en face structural SS-OCT and corresponding B-scans showed resolution of PAMM. Along with a review of the literature on toxoplasmosis-related RAOs, we present the first case of delayed-onset RAO in ocular toxoplasmosis.
The Development of Suspended Scattering Particles in Motion in a Patient with Exudative Reticular Pseudodrusen
Authors: Durlu Yusuf Kemal
Published: October 2023

The development and characteristics of suspended scattering particles in motion (SSPiMs) in a patient with exudative reticular pseudodrusen (ERPD) are reported using multimodal imaging modalities. An 82-year-old woman was referred because of persistent macular edema during intravitreal injections of bevacizumab. ERPD associated with types I and II (mixed type) macular neovascularization in both eyes was diagnosed. Bilateral flat irregular pigment epithelial detachments were associated with macular neovascularization in both eyes by optical coherence tomography. An intense oval hypersignal was found at umbo in her right eye, as detected by en face optical coherence tomography angiography. This avascular hypersignal at umbo was SSPiM. No change was noticed in the appearance of SSPiM after intravitreal injection of aflibercept. However, intraretinal hemorrhage developed in Henle’s fiber layer a month after the second intravitreal injection of aflibercept. Then, several SSPiMs were unveiled in a perifoveal location a month after uncomplicated cataract surgery. The SSPiMs that developed after cataract surgery were connected to the capillaries in the deep retinal vascular plexus. Temporary SSPiMs could be seen during injections of anti-vascular endothelial growth factor and after cataract surgery in the same eye of a patient with ERPD. SSPiMs detected by optical coherence tomography angiography were neither artifacts nor hypersignals due to neovascularized vessels. SSPiMs were considered to be a unique phase colloidal phenomenon generating pseudoflow in exudative macular disorders.
Long-Term Outcomes following Intravitreal Ranibizumab for Choroidal Neovascularization Related to Nd:YAG Laser Macular Injury: A Case Report
Authors: Christodoulou Eleni , Batsos Georgios , Christou Evita Evangelia , Gorgoli Konstantina , Parikakis Efstratios , Karagiannis Dimitrios , Kontomichos Loukas , Stefaniotou Maria
Published: October 2023

Choroidal neovascularization (CNV) secondary to Nd:YAG laser macular injury consists of a rare condition without standardized treatment. Herein, we present the long-term outcomes of a case with a spontaneous closure of a laser-associated macular hole that was followed by late-onset CNV and was successfully treated with intravitreal ranibizumab. A 32-year-old man suffered a macula injury in his right eye after accidental exposure to an 800-nm wave length Nd:YAG laser pulse. Ophthalmological examination demonstrated deterioration in visual acuity along with parafoveal and post-hyaloid hemorrhage. After 1 month, fundoscopy indicated the formation of a full-thickness macular hole. A close observation revealed spontaneous closure of the hole and visual improvement within the next month. One and a half year later, the patient presented with sudden visual distortion, while optical coherence tomography and fluorescein angiography disclosed the development of CNV. The patient was successfully treated with a single intravitreal injection of ranibizumab. The patient’s condition has remained stable during an 8-year follow-up period. In conclusion, laser-induced macular injury consists of an increasingly remarkable condition that may have a profound impact on visual outcomes. Our case provides insight into the potential mechanisms of Nd:YAG laser injury and its complications, indicating that CNV may occur even in the long term, while anti-vascular endothelial growth factor may help maintain stable anatomic and functional outcomes.
A Case of Binocular Metastatic Choroidal Tumor Originating from Pulmonary Adenocarcinoma Successfully Treated with Molecular Target Therapy
Authors: Yamaoka Masataka , Igarashi Tsutomu , Shiratori Naka , Miyadera Keiki , Sugano Teppei , Noro Rintaro , Takahashi Hiroshi
Published: October 2023

The occurrence of ocular metastasis from lung cancer is uncommon. In our current case, we report on a 64-year-old male patient found to have metastatic lesions in both choroids after being diagnosed with lung adenocarcinoma. As the patient was found to have a mutation in the epidermal growth factor receptor (EGFR), he was treated with the EGFR tyrosine kinase inhibitor (EGFR TKI), afatinib. However, the treatment response suggested the presence of a progressive disease. Thus, due to cancerous meningitis, the patient’s treatment was changed from afatinib to erlotinib, in addition to adding bevacizumab. Although the general condition of the patient did not change, improvement was noted for the choroidal metastasis. Moreover, the drug change also resulted in an improvement of the visual power of both eyes. Therefore, the results for this patient suggest that systemic administration of erlotinib and bevacizumab may be an effective treatment that leads to morphological and functional improvement in choroidal metastasis cases.
Ocular Syphilis with Retinal and Disc Neovascularization Treated with Bevacizumab: A Case Report
Authors: Comastri Lucia , Heredia Milagros , Bar Diego , Iribarren Guillermo , Schlaen Ariel
Published: October 2023

We report the findings observed in a young woman with ocular syphilis complicated with retinal and disc neovascularization successfully treated with intravitreal bevacizumab. Fluorescein angiography revealed in both eyes intense hyperfluorescence at the level of the disc, multifocal venous wall staining, multifocal paravenous leakage, multiple peripheral saccular venular dilations, diffuse retinal and macular edema, and retinal and disc neovascularization. There was no evidence of retinal ischemia in both eyes. After antibiotic and corticosteroid treatment, the neovascularization persisted in both eyes. Three consecutive doses of intravitreal bevacizumab were administered, with total regression of the retinal and disc neovascularization. Disc and retinal neovascularization along with nonocclusive retinal vasculitis may be a form of presentation of ocular syphilis. Combination of specific treatment, oral corticosteroids, and intravitreal bevacizumab may be useful for treating this clinical manifestation.
Eyelid Soft Tissue Chondroma: A Case Report
Authors: AlHazzani Abeer A. , Malaikah Rawan H. , Altahan Faisal A. , Arafah Maria A. , Al-Faky Yasser H.
Published: October 2023

Soft tissue chondromas are rare benign tumors that occur in extraosseous and extra-synovial locations. We report herein a rare presentation of eyelid soft tissue chondroma in a 45-year-old male presented with a 2-year history of a slowly enlarging subcutaneous firm mass on the left upper eyelid, and complete excision of the lesion followed by histopathological examination rendered the diagnosis of soft tissue chondroma.
Comparison between the Effects of Allopurinol and Febuxostat on the Survival of Patients on Maintenance Hemodialysis
Authors: Kang Seok Hui , Kim Bo Yeon , Son Eun Jung , Kim Gui Ok , Do Jun Young
Published: October 2023

Introduction: There were insufficient pieces of evidence regarding the effect of the two drugs (allopurinol and febuxostat) on patient survival in hemodialysis (HD) patients. Herein, we aimed to compare the efficacy of uric acid-lowering drugs (ULDs) or the type of the drug on patient survival using a representative sample of maintenance HD patients in South Korea. Methods: This study used data from a national HD quality assessment program and the claims data. Use of ULDs was defined as more than one prescription during the 6 months of each HD quality assessment period. The patients were divided into three groups. Patients who were not prescribed allopurinol or febuxostat were included in group 1 (n = 43,251); patients who were prescribed allopurinol were included in group 2 (n = 9,987); and patients who were prescribed febuxostat were included in group 3 (n = 2,890). Results: Kaplan-Meier curves showed that the survival rate was greatest in group 3 and worst in group 1 among the three groups. Multivariable analysis showed that group 2 had better patient survival compared to group 1; however, there was no significant difference in patient survival between groups 2 and 3. In addition, patients with hyperuricemia or gout had better patient survival compared to those without these diseases. Conclusions: Our study showed that survival in patients receiving ULDs was not inferior to that of those not receiving ULDs. Patient survival between patients on HD receiving allopurinol and those receiving febuxostat was similar.
Tolerability and Efficacy of a 10:25 Preparation of Δ9-Tetrahydrocannabinol and Cannabidiol for Treatment of Chronic Back or Neck Pain: A Multiple-Dose Escalation Study
Authors: Glare Paul , Chye Richard , Bloch Mark , Arya Mark , Moore Andrew , Montgomery John
Published: October 2023

Introduction: The aim was to demonstrate the safety and tolerability of cannabidiol (CBD) with Δ9-THC in patients with moderate to severe chronic back or neck pain unresponsive to over-the-counter non-opioid analgesics. Methods: This was a non-randomized, single-arm, open-label study. Participants received escalating doses of an oromucosal-administered combination containing 10 mg/mL of Δ9-THC, 25 mg/mL of CBD. On day 1, patients received once-daily 0.5 mL Cybis® 10:25 (5 mg Δ9-THC plus 12.5 mg CBD daily), escalated at days 8, 15, and 22 to 0.5 mL twice-daily (bd) (10 mg Δ9-THC plus 25 mg CBD daily), 1.0 mL bd (20 mg Δ9-THC plus 50 mg CBD daily), and 1.5 mL bd (30 mg Δ9-THC plus 75 mg CBD daily), respectively. The primary outcome was safety and tolerability, with secondary objectives including pharmacokinetic and efficacy outcomes. Results: 28 patients were enrolled in the study. Their median age was 63.3 years, and half were female. The median history of neck/back pain was 10 years. The pharmacokinetics following single doses of 0.5 mL were variable; however, there were dose-dependent increases in trough levels of CBD and Δ9-THC. Cybis® 10:25 was well tolerated, with the majority of adverse events of mild severity. The most common adverse events were nausea, vomiting, fatigue, dizziness, headache, paresthesia, and anxiety. There were dose-dependent improvements in numerical pain rating scores (p < 0.001), with clinically significant reductions in pain at 1.0 mL bd and 1.5 mL bd doses (28.8% and 34.1% reductions, respectively, p < 0.001). Depressive symptoms and stress had dose-dependent reductions (p = 0.0182, p < 0.01, respectively). Conclusion: In patients with chronic neck/back pain, CBD and Δ9-THC are well tolerated and doses of 1.0 mL bd and 1.5 mL bd showed clinically significant reductions in pain compared to baseline pain scores.
Delayed Bacterial Endotheliitis and Endophthalmitis 11 Years after Cataract Surgery
Authors: Poon Elisabeth , Poon Alexander , McKelvie Penelope , Levitz Lewis , Zamir Ehud
Published: October 2023

Infective endophthalmitis is an uncommon complication following intraocular surgery. Chronic endophthalmitis may present some time after intraocular surgery, making the diagnosis challenging. Cutibacterium acnes is a well-recognised causative agent of these chronic infections. Practitioners should be aware of the conditions required to culture this slow-growing organism. We report a case of delayed low-grade endophthalmitis presenting 11 years after cataract surgery. Cutibacterium acnes and Staphylococcus warneri were cultured from Descemet’s membrane biopsy following three failed previous attempts at microbiological studies. Clinical features of the infection included discrete white granules on the iris, endothelium, and within the capsular bag of the patient’s right eye. The patient presented with no signs of systemic infection and the left eye was normal on examination. Bullous keratopathy, secondary to endothelial dysfunction was a feature of this infection. This retrospective case report illustrates the prolonged periods for which Cutibacterium acnes can remain latent before causing clinical signs. While uncommon, endothelial involvement may occur and clinicians should consider low-grade infective endophthalmitis in cases with corneal oedema.
Long-Term, Self-Dosing CBD Users: Indications, Dosage, and Self-Perceptions on General Health/Symptoms and Drug Use
Authors: Kaufmann Robert , Harris Bozer Amber , Jotte Amanda Kube , Aqua Keith
Published: October 2023

Introduction: Self-dosing of off-the-shelf cannabidiol (CBD) for a myriad of health conditions is common in the USA. These CBD products are often mislabeled, suggesting that much less or much more CBD is being consumed than indicated on the label. This study examined the relationship between long-term self-dosing of CBD and (a) indications and, when a verified concentration of CBD is being consumed, (b) the daily CBD dosage, (c) the impact on general health and symptoms, and (d) over-the-counter (OTC) and prescription (Rx) drug usage. Methods: US adults 18–75 years of age who had used unverified CBD products for >1 month were recruited to participate in this decentralized, observational, IRB-approved study and provided a concentration-verified CBD product of their choice from 15 different vendors for 4 weeks. Prior to receiving product, they were queried on their primary reason for use (PRfU), primary symptom for use (PSfU), general health score (GHS), symptom score (SS), OTC and Rx drug use, and daily CBD dose. Individuals were queried daily on OTC and Rx drug use and CBD dose and weekly on SS and GHS prior to (pre-CBD) and after (post-CBD) ingestion of CBD on that day. Results: The PRfU included chronic pain, mental health, general health and wellness, sleep disorders, the central nervous system, digestive health, and others, while the PSfU included anxiety, back and/or joint pain, sleep, inflammation, and others. The mean daily dose was normally distributed, with a mean, median, and range of 53.1, 40.8, 8–390 mg/day, respectively. For both GHS and SS, the post-CBD was significantly higher than the pre-CBD score for each category of PRfU. The GHS scores did not change over the study, but pre- and post-CBD SS improved over time, with pre-improving more than post-CBD SS. The percentage of individuals decreasing or completely stopping OTC drugs or Rx drugs over the 4 weeks was 31.2% and 19.2%, respectively, with those taking CBD for chronic pain, decreasing drug use the most. OTC and Rx drug usage decreased when the CBD dose was changed and when GHS and SS improved. Conclusion: Pain, mental health (primarily anxiety/stress), and sleep are the most common reasons for CBD use. Self-administration of CBD reduced OTC and Rx drug usage at daily doses less than those reported in controlled studies. CBD self-administration significantly improves self-perception of general health and decreases symptom severity, and as these improve, fewer OTC and Rx drugs are used.
Medical Cannabis Alleviates Chronic Neuropathic Pain Effectively and Sustainably without Severe Adverse Effect: A Retrospective Study on 99 Cases
Authors: Kluwe Lan , Scholze Christian , Schmidberg Lisa Marie , Wichmann Julian Lukas , Gemkov Mihail , Keller Martin Julian , Farschtschi Said C.
Published: October 2023

Introduction: Medical cannabis may provide a treatment option for chronic neuropathic pain. However, empirical disease-specific data are scarce. Methods: This is a retrospective observational study including 99 patients with chronic neuropathic pain. These patients received medical cannabis by means of inhaling dried flowers with tetrahydrocannabinol content of <12–22% at a maximal daily dose of 0.15–1 g. Up to six follow-ups were carried out at intervals of 4–6 weeks. Pain severity, sleep disturbance, general improvement, side effects, and therapy tolerance at the follow-up consultations were assessed in interviews and compared with the baseline data using non-parametric Wilcoxon signed-rank test. Results: Within 6 weeks on the therapy, median of the pain scores decreased significantly from 7.5 to 4.0 (p < 0.001). The proportion of patients with severe pain (score >6) decreased from 96% to 16% (p < 0.001). Sleep disturbance was significantly improved with the median of the scores decreased from 8.0 to 2.0 (p < 0.001). These improvements were sustained over a period of up to 6 months. There were no severe adverse events reported. Mild side effects reported were dryness in mucous tissue (5.4%), fatigue (4.8%), and increased appetite (2.7%). Therapy tolerance was reported in 91% of the interviews. Conclusion: Medical cannabis is safe and highly effective for treating neuropathic pain and concomitant sleep disturbance.
Mobilization Strategies in Myeloma Patients Intended for Autologous Hematopoietic Cell Transplantation
Authors: Jantunen Esa , Partanen Anu , Turunen Antti , Varmavuo Ville , Silvennoinen Raija
Published: October 2023

Background: Multiple myeloma is currently the leading indication for autologous hematopoietic cell transplantation (AHCT). A prerequisite for AHCT is mobilization and collection of adequate blood graft to support high-dose therapy. Current mobilization strategies include granulocyte colony-stimulating factor (G-CSF) alone or in combination with chemotherapy most commonly cyclophosphamide (CY). More recently, plerixafor has become into agenda especially in patients who mobilize poorly. In the selection of a mobilization method, several factors should be considered. Summary: Preplanned collection target is important as G-CSF plus plerixafor is more effective in the mobilization of CD34+ cells than G-CSF alone. On the other hand, CY plus G-CSF is superior to G-CSF only mobilization. Previous therapy and age of the patients are important considerations as G-CSF alone may not be effective enough in patients with risk factors for poor mobilization. These factors include extensive lenalidomide exposure, irradiation to bone marrow-bearing sites, higher age, or a previous mobilization failure. Also, local preferences and experiences as well as the number of apheresis needed are important issues as well as cost-effectiveness considerations. Mobilization method used may have implication for cellular composition of collected grafts, which might have an impact on posttransplant events such as hematologic and immune recovery in addition to also potential long-term outcomes. Key Message: Currently, G-CSF alone and preemptive plerixafor if needed might be considered as a standard mobilization strategy in MM patients intended for AHCT.
Management of Nonmalignant Portal Vein Thrombosis in Cirrhosis
Authors: Capinha Francisco , Noronha Ferreira Carlos
Published: October 2023

Nonmalignant portal vein thrombosis (PVT) is a common complication of cirrhosis especially at the stage of decompensations. The diagnosis of PVT in cirrhosis is often incidental and it may be detected during routine semestral abdominal ultrasound with Doppler during screening for hepatocellular carcinoma or during hospitalization for decompensated cirrhosis. After detection of PVT on abdominal ultrasound, it is important to evaluate patients with cross-sectional imaging to determine the age of thrombus, whether acute or chronic, the extent and degree of luminal occlusion of the portal vein, and to rule out hepatocellular carcinoma or other underlying malignancy. Factors influencing management include the degree and extent of luminal occlusion of PVT, potential listing for liver transplantation, and portal hypertension (PHT) complications such as variceal hemorrhage and refractory ascites, severity of thrombocytopenia, and other comorbidities including chronic kidney disease. Anticoagulation is the most common therapeutic option and it is specially indicated in patients who are candidates for liver transplantation. Interventional procedures including transjugular intrahepatic portosystemic shunt (TIPS) placement and mechanical thrombectomy may be used on a case-by-case basis in patients with contraindications or adverse events related to anticoagulation, who develop worsening PVT while on anticoagulant therapy, or have chronic PVT and PHT complications that are not manageable medically or endoscopically.
Management of Large Conjunctival Cysts in a Patient with Stevens-Johnson Syndrome: A Case Report and Review of the Literature
Authors: Hooshmandi Sadid , Hassanpour Kiana , Veisi Amirreza , Movafaghi Vahid , Langari Farideh , Sadoughi Mohammad-Mehdi , Javadi Mohammad Ali
Published: October 2023

Stevens-Johnson syndrome (SJS) is a life-threatening mucocutaneous disease with various etiologies including drugs, infections, and malignancies. Ocular manifestations of SJS vary from the membrane, symblepharon formation, and epithelial defect in the acute phase to trichiasis, eyelid margin keratinization, and lacrimal duct obstruction in the chronic phase. A 13-year-old boy with a history of drug-induced SJS presented to our clinic complaining of a mass in the nasal side and inferior fornix of the right eye from 1 year ago. The mass-like lesion in the medial side of the right eye was accompanied by ankyloblepharon, symblepharon, and ptosis and limited ocular movement. Orbital imaging showed cystic lesions on the medial side of the right globe and the inferior fornix. Two large cysts were entirely surgically excised. Histopathologic investigation revealed conjunctival tissue with nonkeratinized epithelium and goblet cells. There was no sign of conjunctival cyst recurrence or symblepharon formation on the 6th-month follow-up. The inferior fornix achieved acceptable depth and the ocular movements became normal.
Impact of Intensity of Continuous Renal Replacement Therapy on Duration of Ventilation in Critically Ill Patients: A Secondary Analysis of the RENAL Trial
Authors: Serpa Neto Ary , Naorungroj Thummaporn , Gallagher Martin , Bellomo Rinaldo
Published: October 2023

Introduction: More intensive renal replacement therapy (RRT) has been associated with prolonged mechanical ventilation (MV). However, such finding may be dependent on RRT modality. We hypothesized that, when using continuous renal replacement therapy (CRRT), RRT intensity would not be associated with prolonged MV. Methods: In a secondary analysis of the Randomized Evaluation of Normal versus Augmented Level (RENAL) Replacement trial comparing different CRRT intensities, we applied Fine-Gray competing risk analysis with time to successful extubation within 28 days as primary outcome. Results: We studied 531 patients in the higher intensity and 551 in the lower intensity group. Higher intensity patients had more hypophosphatemia (66.7 vs. 58.1%; p = 0.004) and more days with hypophosphatemia (2.2 ± 2.8 vs. 1.6 ± 2.2; p < 0.001). There was no difference in the number of patients extubated within 28 days (60.1% vs. 62.4%; adjusted subdistribution hazard ratio [SHR], 0.95 [95% CI, 0.86 to 1.06]) or time to extubation (8 [5–16] vs. 8 [5–15] days; adjusted median difference, 0.65 [95% CI, −0.41 to 1.70]). Among patients from the upper tertile of days with hypophosphatemia, higher intensity CRRT was associated with a lower chance of successful extubation within 28 days (SHR, 0.67 [95% CI, 0.55 to 0.82]; p for heterogeneity = 0.013). Conclusions: In the RENAL trial, higher intensity CRRT was not associated with delayed extubation. However, it was associated with a greater rate of hypophosphatemia and more days with hypophosphatemia was associated with a lower chance of successful extubation.
Three Pediatric Patients with Congenital Nephrogenic Diabetes Insipidus due to AVPR2 Nonsense Mutations and Different Clinical Manifestations: A Case Report
Authors: Watanabe Hijiri , Tamura Hiroshi , Furuie Keishiro , Kuraoka Shohei , Nakazato Hitoshi
Published: October 2023

Congenital nephrogenic diabetes insipidus (CNDI), a rare hereditary disorder, is characterized by the inability of the kidneys to concentrate urine in response to the antidiuretic hormone arginine vasopressin (AVP); as a result, large volumes of unconcentrated urine are excreted. In addition to the clinical manifestations of CNDI, such as dehydration and electrolyte disturbances (hypernatremia and hyperchloremia), developmental delay can result without prompt treatment. In approximately 90% of cases, CNDI is an X-linked disease caused by mutations in the arginine vasopressin receptor 2 (AVPR2) gene. In approximately 9% of cases, CNDI is an autosomal recessive disease caused by mutations in the water channel protein aquaporin 2 (AQP2), and 1% of cases are autosomal dominant. We report a case of CNDI caused by a novel AVPR2 nonsense mutation, c.520C>T (p.Q174X), and cases of siblings in another family who had a different AVPR2 nonsense mutation, c.852G>A (p.W284X). Both cases responded well to treatment with hydrochlorothiazide and spironolactone. If CNDI is suspected, especially in carriers and neonates, aggressive genetic testing and early treatment may alleviate growth disorders and prevent irreversible central nervous system disorders and developmental delay.
Exame de Papanicolaou no Brasil: análise da Pesquisa Nacional de Saúde em 2013 e 2019
Authors: Azevedo e Silva Gulnar , Damacena Giseli Nogueira , Ribeiro Caroline Madalena , Alcantara Luciana Leite de Mattos , Souza Júnior Paulo Roberto Borges de , Szwarcwald Célia Landmann
Published: October 2023

OBJETIVOS: Comparar a cobertura do rastreamento do câncer de colo do útero no Brasil em 2013 e 2019, investigar os fatores associados à realização do exame e os motivos informados para não ter realizado, além de comparar o tempo do recebimento do resultado do exame no SUS e na rede privada. MÉTODOS: A partir de dados da Pesquisa Nacional de Saúde (PNS) foram calculadas as prevalências e os respectivos intervalos de confiança de realização do exame preventivo do câncer do colo do útero há menos de três anos, em mulheres de 25 a 64 anos, em 2013 e 2019. Modelos de regressão de Poisson foram utilizados para comparar as prevalências do desfecho segundo características sociodemográficas. Também foram analisados os motivos para não ter feito o exame e o tempo entre a realização e o recebimento do laudo. RESULTADOS: Houve aumento na cobertura do exame preventivo no Brasil entre 2013 (78,7%) e 2019 (81,3%) e redução na proporção de mulheres que nunca fizeram o exame de 9,7% para 6,1%. A prevalência de realização do exame foi maior em mulheres brancas, melhor escolaridade e renda mais alta, residentes nas regiões Sul e Sudeste. Os motivos mais frequentes para não realizar o exame foram achar desnecessário (45% em 2013 e em 2019) e nunca ter sido orientada a fazê-lo (20,6% em 2013 e 14,8% em 2019). CONCLUSÕES: Apesar das elevadas coberturas de rastreamento alcançadas pelo país, há grande desigualdade no acesso ao exame, e uma parcela não desprezível de mulheres está sob maior risco de morrer por uma doença que pode ser evitada. Esforços devem ser feitos para a estruturação de um programa de rastreamento organizado que identifique e capte as mulheres mais vulneráveis.
Coleção Entomológica de Referência: 85 anos de contribuições à saúde pública
Authors: Dolci Mariana de Carvalho , Spina Fabrício Auad , Sallum Maria Anice Mureb
Published: October 2023

O Departamento de Higiene da Faculdade de Medicina de São Paulo (FMUSP), organizado com o apoio da Fundação Rockefeller, tornou-se o Instituto de Higiene, tendo a aula inaugural ministrada por Samuel Darling em 1918. A história da Entomologia de Saúde Pública confundese com a do próprio Instituto, que passou a ser a Faculdade de Higiene e Saúde Pública em 1945. Ainda na década de 1930, Paulo César de Azevedo Antunes e John Lane começam a organizar a Entomologia de Saúde Pública dentro da Parasitologia Médica, do então Instituto de Higiene. Durante esse período o laboratório de entomologia passou a ser reconhecido por suas pesquisas em sistemática de insetos hematófagos, bem como na ecologia, biologia e comportamento de vetores. A Coleção Entomológica de Referência (CER) originou-se naturalmente das pesquisas de Paulo César Antunes e John Lane e é um patrimônio nacional e internacional abrangendo tipos primários e secundários de espécies de insetos que apresentam interesse à saúde pública. No decorrer dos anos, consolidou-se com os esforços de Augusto Ayroza Galvão, Renato Corrêa, José Coutinho, Nelson Cerqueira, Ernesto Rabello, Oswaldo Forattini e outros. Em seus mais de oitenta anos de atividades, a CER possibilitou a formação de diversos cientistas aptos a atuar em programas de vigilância e controle de endemias associadas aos insetos vetores em toda a América Latina, além de formar taxonomistas voltados aos insetos de interesse em Saúde Pública. Pesquisadores de outros institutos brasileiros e do exterior juntaram-se ao laboratório de entomologia por conta de sua importância e das pesquisas nele desenvolvidas. A produção científica crescente possibilitou aos estudos entomológicos desenvolvidos na Faculdade de Saúde Pública (FSP) adquirirem uma visibilidade internacional, contribuindo para o desenvolvimento das ações de prevenções de doenças e controle de epidemias no país.
Mortalidade hospitalar por covid-19 em crianças e adolescentes no Brasil em 2020–2021
Authors: Silva Amanda Cilene Cruz Aguiar Castilho da , Luiz Ronir Raggio , Moraes José Rodrigo de , Rocha Pedro Henrique Vieira , Zeitoune Regina Célia Gollner , Barbosa Arnaldo Prata , Moreira Jessica Pronestino de Lima
Published: October 2023

OBJETIVO: Descrever casos, óbitos e mortalidade hospitalar por covid-19 em crianças e adolescentes no Brasil, conforme faixa etária, durante as fases de evolução da pandemia em 2020 e 2021. MÉTODOS: Censo de pacientes de até 19 anos internados com síndrome respiratória aguda grave, por covid-19 ou não especificada, notificados ao Sistema de Informação de Vigilância Epidemiológica da Gripe do Brasil, entre 1 de janeiro de 2020 e 31 de dezembro de 2021. Os dois anos foram divididos em seis fases, abrangendo a disseminação da doença − primeira, segunda e terceira onda −, bem como o impacto da vacinação. A população pediátrica foi categorizada em lactentes, pré-escolares, escolares e adolescentes. A mortalidade hospitalar foi avaliada por fase da pandemia e faixa etária. RESULTADOS: Foram contabilizados 144.041 pacientes nos dois anos, sendo 18,2% casos de covid-19 confirmados. Menores de 5 anos (lactentes e pré-escolares) corresponderam a 62,8% dos hospitalizados. Evoluíram a óbito 4.471, representando cerca 6,1 óbitos por dia. Os lactentes foram os que mais evoluíram para unidade de terapia intensiva (24,7%) e apresentaram o maior número bruto de óbito (n = 2.012), porém a mortalidade foi maior entre os adolescentes (5,7%), chegando a 9,8% na fase 1. O primeiro pico de óbitos ocorreu na fase 1 (maio/2020), e outros dois picos ocorreram na fase 4 (março/2021 e maio/2021). Verificou-se avanço de casos e óbitos para as idades inferiores desde a fase 4. A mortalidade hospitalar na população pediátrica foi maior nas fases 1, 4 e 6, acompanhando os fenômenos de disseminação/interiorização do vírus no país, início da segunda onda e início da terceira onda, respectivamente. CONCLUSÃO: O número absoluto de casos de covid-19 em crianças e adolescentes é expressivo. Embora a vacinação completa em ordem decrescente de idade tenha proporcionado um desvio natural de faixa etária, ocorreu um distanciamento maior entre a curva de novos casos hospitalizados e a curva de óbitos, indicando o impacto positivo da imunização.
Efficacy, Safety, and Tolerability of Inclisiran in Patients With Homozygous Familial Hypercholesterolemia: Results From the ORION-5 Randomized Clinical Trial
Authors: Raal Frederick , Durst Ronen , Bi Ran , Talloczy Zsolt , Maheux Pierre , Lesogor Anastasia , Kastelein John J.P. ,   on behalf of the ORION-5 Study Investigators
Published: October 2023

BACKGROUND:

Homozygous familial hypercholesterolemia is a genetic disease characterized by extremely high levels of low-density lipoprotein cholesterol (LDL-C) and a high risk of premature cardiovascular events. The proof-of-concept study ORION-2 (A Study of Inclisiran in Participants With Homozygous Familial Hypercholesterolemia) showed that inclisiran, a small interfering RNA that prevents production of the hepatic PCSK9 protein (proprotein convertase subtilisin/kexin type 9), could lead to durable reductions in LDL-C levels when added to statins and ezetimibe in patients with homozygous familial hypercholesterolemia.

METHODS:

ORION-5 was a phase 3, 2-part, multicenter study in 56 patients with homozygous familial hypercholesterolemia and elevated LDL-C levels despite maximum tolerated doses of LDL-C–lowering therapies with or without lipoprotein apheresis. Patients eligible for part 1 (double-blind, 6 months) were randomized 2:1 to receive either 300 mg of inclisiran sodium (equivalent to 284 mg of inclisiran) or placebo. Placebo-treated patients from part 1 were transitioned to inclisiran in part 2 (open-label, 18 months). The primary end point was the percentage change in LDL-C levels from baseline to day 150.

RESULTS:

The mean age of the patients was 42.7 years, and 60.7% were women. The mean baseline LDL-C levels were 294.0 mg/dL and 356.7 mg/dL in the inclisiran and placebo groups, respectively. The placebo-corrected percentage change in LDL-C level from baseline to day 150 was −1.68% (95% CI, −29.19% to 25.83%;
P
=0.90), and the difference was not statistically significant between the inclisiran and placebo groups. The placebo-corrected percentage change in PCSK9 levels from baseline to day 150 was −60.6% with inclisiran treatment (
P
<0.0001); this was sustained throughout the study, confirming the effect of inclisiran on its biological target of PCSK9. No statistically significant differences between the inclisiran and placebo groups were observed in the levels of other lipids and lipoproteins (apolipoprotein B, total cholesterol, and non−high-density lipoprotein cholesterol). Adverse events and serious adverse events did not differ between the inclisiran and placebo groups throughout the study.

CONCLUSIONS:

Inclisiran treatment did not reduce LDL-C levels in patients with homozygous familial hypercholesterolemia despite substantial lowering of PCSK9 levels. Inclisiran was well-tolerated, and the safety findings were consistent with previously reported studies and the overall safety profile.

REGISTRATION:

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT03851705.
Remote Ischemic Conditioning and Outcomes in Acute Ischemic Stroke With Versus Without Large Artery Atherosclerosis
Authors: Cui Yu , Yuan Zhi-Mei , Liu Quan-Ying , Wang Ying-Jia , Chen Hui-Sheng
Published: October 2023

BACKGROUND:

RICAMIS trial (The Remote Ischemic Conditioning for Acute Moderate Ischemic Stroke) has demonstrated efficacy of remote ischemic conditioning (RIC) in acute ischemic stroke. We conducted a post hoc analysis of RICAMIS to investigate whether large artery atherosclerosis (LAA) subtype contributed to the outcomes.

METHODS:

This is a post hoc analysis of the RICAMIS trial. Patients randomized to RIC group and Control group in full analysis set of RICAMIS were classified into LAA and non-LAA subtypes. The primary outcome was excellent functional outcome at 90 days, defined as modified Rankin Scale score of 0 to 1. Compared with patients receiving usual care, we investigated the association of RIC effect with outcomes in stroke subtypes and the interaction between RIC effect and stroke subtypes. The primary analysis was adjusted analysis.

RESULTS:

Among 1773 patients, 516 were assigned to LAA subtype (229 in the RIC group and 287 in the control group) and 1257 to non-LAA subtype (633 in the RIC group and 624 in the control group). Median age was 65 years, and 34.2% were women. A higher proportion of primary outcome was found to be associated with RIC treatment in LAA subtype (adjusted risk difference, 11.4% [95% CI, 3.6%–19.2%];
P
=0.004), but not in non-LAA subtype (adjusted risk difference, 4.1% [95% CI, −1.1% to 9.3%];
P
=0.12). There was no significant interaction between RIC effect and stroke subtypes (
P
=0.12).

CONCLUSIONS:

Patients with LAA subtype may benefit from RIC after stroke with respect to excellent functional outcome at 90 days.

REGISTRATION:

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT03740971.
The Works of Alan Richardson as a Prototype Public Theology
Authors: Root Terence George
Published: October 2023

Public theology today is a discipline engaging with an ever-growing array of publics, seeking to view their various social, political and cultural issues through a theological lens. In this article I will argue that the discipline has often failed to pay attention to earlier work which can claim to be antecedent of the genre. To evidence this claim I will describe and contextualise the work of Alan Richardson in mid twentieth-century Britain as a pragmatic endeavour responding to a developing public antipathy towards Christian beliefs and adherence which can be viewed as a prototype public theology. I will suggest that engaging with Richardson’s work perceived as an antecedent of public theology will add praxis to contemporary debates focused on theory, definitions and purposes.
Parapsychology, Hallucinations, Collective Delusions, and Jesus’ Post-Resurrection Appearances
Authors: Smith Stephen H.
Published: October 2023

After a brief outline of Glenn Siniscalchi’s apology for the traditional approach to the post-resurrection appearances, I examine his particular view that any attempt to compare the appearances of Jesus with the various apparitions discussed by parapsychologists is doomed to failure. Siniscalchi states, correctly, that the only category of apparitions worthy of consideration at all is the ‘post-mortem apparition’. However, some of the suggested differences between these and the appearances of Jesus seem somewhat banal, and are not as significant as they are made out to be. My suggestion is that some form of hypothesis coupling hallucinations with collective delusions would explain both individual and collective post-resurrection appearances, and serve as a viable alternative to the traditional evangelical view.
When Is a Belief Formed in an Epistemically Circular Way?
Authors: Stewart Todd M.
Published: October 2023

While there has been a great deal of discussion of whether and when beliefs formed in an epistemically circular manner can be justified, there has been almost no discussion of exactly which beliefs are formed in a circular manner. These discussions have tended to focus on an extremely limited number of intuitively-identified paradigm examples concerning attempts to establish the reliability of a method of belief formation. Here, I seek to answer a prior analytical question about the nature of epistemic circularity by developing a criterion which sorts epistemically circular beliefs from non-epistemically circular beliefs.