Additional Cases Research Articles

Perioperative Recommendations for Corneal Refractive Surgery Patients With Inherited Bleeding Disorders.

To synthesize the current literature regarding patients with inherited bleeding disorders and suggest comprehensive evaluation and preoperative recommendations for these patients before undergoing corneal refractive surgery. The literature search was conducted through PubMed, Embase, and Google Scholar databases for publications through January 4, 2024 for reports of ocular bleeding manifestations in patients with inherited bleeding disorders and reports of patients without a history of bleeding disorders who had intraoperative or postoperative hemorrhagic complications with corneal refractive surgery. Additional cases from the literature and a retrospective chart review at a corneal practice were obtained describing patients with inherited bleeding disorders who underwent corneal refractive surgery. Four articles were found detailing ocular bleeding manifestations in patients with inherited bleeding disorders who underwent ocular surgery other than corneal refractive surgery. Thirty articles were found detailing intraoperative and postoperative bleeding manifestations in patients without a history of inherited bleeding disorders who underwent corneal refractive surgery. Eight cases (3 patients from the literature search and 5 patients from a retrospective chart review) were found regarding patients with inherited bleeding disorders who underwent corneal refractive surgery. For corneal refractive surgery with topical anesthesia, the perioperative risk and need for any hemostasis intervention in individuals with an inherited bleeding disorder depends on the type of disorder, status of preoperative factor level concentrations, or a prior history of bleeding. If required, clotting factor optimization should be tailored to each candidate on a case-by-case basis.

Clinically significant prostate cancer detection rate in biopsy-naïve patients with mpMRI and microultrasound topographically discordant lesions: A single-center retrospective analysis

Introduction and objectivesMultiparametric magnetic resonance imaging (mpMRI) has improved the detection of clinically significant prostate cancer (csPCa), and microultrasound (micro-US) shows promise in enhancing detection rates. We compared mpMRI-guided targeted biopsy (MTBx) and micro–US-guided targeted biopsy (micro–US-TBx) in biopsy-naïve patients with discordant lesions at micro-US and mpMRI to detect csPCa (grade group ≥2) and clinically insignificant PCa (ciPCa; grade group 1) and assessed the role of nontargeted systematic biopsy (SBx). Material and MethodsWe analyzed 178 biopsy-naive men with suspected PCa and discordant lesions at mpMRI and micro-US. All patients underwent mpMRI followed by micro-US, the latter being performed immediately before the biopsy. Imaging findings were interpreted blindly, followed by targeted and SBx. Median age was 63 years (IQR, 57–70), median prostate-specific antigen level was 7 ng/mL (IQR, 5–9 ng/mL), and median prostate volume was 49 cm^3 (IQR, 35–64 cm^3). Overall, 86/178 (48%) patients were diagnosed with PCa, 51/178 (29%) with csPCa. ResultsMicro-USTBx detected csPCa in 36/178 men (20%; 95% CI: 26–46), and MTBx detected csPCa in 28/178 men (16%; 95% CI: 36–50), resulting in a -8% difference (95% CI: −10, 4; P = 0.022) and a relative detection rate of 0.043. Micro-USTBx detected ciPCa in 9/178 men (5%; 95% CI: 3, 15), while MTBx detected ciPCa in 12/178 men (7%; 95% CI: 5, 20), resulting in a −3% difference (95% CI: −2 to 4; P = 0.2) and a relative detection rate of 0.1. SBx detected ciPCa in 29 (16%) men. mpMRI plus micro-US detected csPCa in 51/178 men, with no additional cases with the addition of SBx. Similarly, MTBx plus micro-USTBx plus SBx detected ciPCa in 35/178 men (20%; 95% CI: 18, 37) compared to 9 (5%) in the micro-US pathway (P = 0.002) and 14/178 (8%; 95% CI: 6, 26) in the mpMRI plus micro-US pathway (P = 0.004). ConclusionsIn conclusion, a combined micro-US/mpMRI approach could characterize primary disease in biopsy-naïve patients with discordant lesions, potentially avoiding SBx. Further studies are needed to validate our findings and assess micro-US's role in reducing unnecessary biopsies.

Infrared signal-based implementation of model-based predictive control (MPC) for cost saving in a campus building

Model-based predictive control (MPC) is an advanced control method that is used to achieve energy and cost savings in building energy management. However, there are various challenges to implementing MPC in actual buildings, such as additional engineering costs, physical damage to systems, and security concerns. This study proposes a non-intrusive implementation method for MPC based on a low-cost communication system. Firstly, a grey-box building model was developed along with the heating, ventilation, and air conditioning (HVAC) models based on the actual measurements of the test building. A simulation case study of MPC was performed, along with baseline feedback control, using these constructed models. The MPC outperformed the feedback control in terms of comfort, electricity consumption, and cost. It was implemented in an actual test zone to demonstrate the feasibility of a low-cost and non-intrusive implementation method that was realized using Arduino-based infrared signal communication and to evaluate the cost-saving potential of the MPC when compared with the baseline control. This experiment was conducted under a confined schedule for occupancy and set-point temperature for three days for the MPC and two days for the baseline feedback control in the cooling season. The cost savings of the MPC are as high as 5.8 %. Additional feedback cases were considered with a non-confined occupancy schedule and set-point temperature. The resulting energy consumption and cost savings are 25.2 % and 33.7 %, respectively. In this study, the applicability of the Arduino-based low-cost and non-intrusive implementation method for MPC was demonstrated, and the actual saving percentage of the MPC was compared with the conventional control method in a real building.

Managing medically refractory elevated intracranial pressure in a pediatric patient on ECMO: illustrative case.

We demonstrate the complexities of managing pediatric patients on extracorporeal membrane oxygenation (ECMO) therapy requiring neurosurgery, focusing on systemic anticoagulation, cardiac function, and medically refractory intracranial pressure (ICP). A 3.5-year-old female with Tetralogy of Fallot developed severe ischemic cerebral edema following post-operative cardiac arrest and required ECMO. This case, along with four additional cases of children requiring neurosurgery while on ECMO, was examined. Emergency neurosurgical intervention in the primary case led to significant improvement, highlighting the delicate balance between managing ECMO-induced anticoagulation and urgent neurosurgical needs. The additional cases had variable outcomes, emphasizing the challenges of caring for these critically ill patients. Successful management of children requiring ECMO support and neurosurgical intervention requires thoughtful multidisciplinary care. This report illustrates some of the nuances in such decision-making, and demonstrates one potential path to a good outcome.

EBV-positive small cell neuroendocrine carcinoma of nasopharynx as a probably unique subtype of neuroendocrine carcinoma: a clinicopathologic study of three cases and literature review

BackgroundThere is currently scarcity of information on small cell neuroendocrine carcinoma of the nasopharynx (SCNEC-nasopharynx). It is believed that this type of cancer is not associated with Epstein-Barr virus (EBV) infection and is indistinguishable from classic SCNEC occurring in other organs.Materials and methodsHerein we provided 3 cases of nasopharyngeal mass in our hospital, two males and one female. On admission, these patients were considered nasopharyngeal carcinoma with lymph node metastasis, and one of them had liver metastasis. The nasopharyngeal mucosal tissues were biopsied for pathological examination including immunohistochemistry and in situ hybridization. PubMed database was searched for articles about SCNEC-nasopharynx published up to April 2024 in any language.ResultThe 3 cases had similar histological features of SCNEC in other organs but differed in rich- tumor-infiltrating lymphocytes (TILs). All of them stained for pancytokeratin (panCK) and epidermal growth factor receptor (EGFR). Case 1 and Case 2 diffusely expressed insulinoma-associated protein 1(INSM-1) and synaptophysin (Syn), Case 3 strongly stained for CD56 and Syn. Immunostaining of all 3 cases for p40, p63, TTF-1, CK20, S-100 and NUT showed negative. BRG-1, INI-1 and Rb were retained. And p53 all showed wild-type expression. The Ki-67 labeling indiced of case 1, 2, and 3 were 80%, 90%, and 80%, respectively. In situ hybridization showed strong and uniform nuclear positivity of EBV-encoded small RNAs (EBER) in the neoplastic cells of 3 cases.ConclusionEBV-positive SCNEC-nasopharynx was exactly rare. The origin of this tumor is still controversial. It may originate from EBV-infected mucosal epithelium like nasopharyngeal carcinoma. Based on our cases and relevant literature, we found EBV-positive SCNEC-nasopharynx as a probably site-specific subtype of SCNEC with differing pathogenetic mechanism. The subtype not only virus positivity but also that it was associated with TILs and did not show p53 or Rb alterations by immunohistochemistry. It may be more responsive to treatment and have a better prognosis than classic SCNEC. We will continue to follow-up these patients and collect additional cases to further understand the unique biology of this rare solid tumor.

A Five-Year Review of Newborn Screening for Spinal Muscular Atrophy in the State of Utah: Lessons Learned.

Spinal muscular atrophy (SMA) is an autosomal recessive condition characterized by alpha motor neuron degeneration in the spinal cord anterior horn. Clinical symptoms manifest in the first weeks to months of life in the most severe cases, resulting in progressive symmetrical weakness and atrophy of the proximal voluntary muscles. Approximately 95% of SMA patients present with homozygous deletion of the SMN1 gene. With multiple available therapies preventing symptom development and slowing disease progression, newborn screening for SMA is essential to identify at-risk individuals. From 2018 to 2023, a total of 239,844 infants were screened. 13 positive screens were confirmed to have SMA. An additional case was determined to be a false positive. We are not aware of any false-negative cases. All patients were seen promptly, with diagnosis confirmed within 1 week of the initial clinical visit. Patients were treated with nusinersen or onasemnogene abeparvovec. Treated patients with two copies of SMN2 are meeting important developmental milestones inconsistent with the natural history of type 1 SMA. Patients with 3-4 copies of SMN2 follow normal developmental timelines. Newborn screening is an effective tool for the early identification and treatment of patients with SMA. Presymptomatic treatment dramatically shifts the natural history of SMA, with most patients meeting appropriate developmental milestones. Patients with two copies of SMN2 identified through newborn screening constitute a neurogenetic emergency. Due to the complexities of follow-up, a multidisciplinary team, including close communication with the newborn screening program, is required to facilitate timely diagnosis and treatment.

Prevalence, clinical presentation, and treatment-management of cerebral venous thrombosis associated with spontaneous intracranial hypotension: A combined case-series and systematic literature review approach.

Cerebral venous thrombosis (CVT) is a rare complication of spontaneous intracranial hypotension (SIH). Therefore, its correct diagnosis and the corresponding optimal treatment-management identification remains challenging. Over the last 10 years, 300 patients received a definite SIH diagnosis at our stroke center. Through thorough review of the database, we identified all patients with SIH-related CVT. In addition, we performed a systematic literature review including all publications on SIH-related CVT. Five out of our 300 SIH patients showed CVT (F/M:2/3, mean age: 51.8 ± 15.7). Through the literature search, 72 additional cases were identified. Overall, the prevalence was 1.3% and main clinical presentations were orthostatic headache, nausea, and vomiting. The CVT was predominantly located at the superior sagittal sinus. Treatment strategies included anticoagulants (ACs) (43%), epidural blood patch (EBP) (19.4%), and combined AC + EBP (33.3%). In our cohort, all but one patient received combined EBP and AC. The mean clinical and radiological follow-up were 2 years and 1.5 years, respectively. Complete clinical recovery was reported in 96% of the cases, whereas 56% showed complete radiological CVT resolution. Among patients without radiological resolution (26.4%), 57% received AC-only, while 43% received combined AC + EBP. Of our five cases, all but one patient received combined AC + EBP. The overall prevalence of SIH-related CVT was 1.3%. AC and combined AC + EBP were the most used treatment-management strategies. CVT resolution was more commonly achieved after the combined strategy. Overall, the rate of complete clinical recovery was 96%.

THE GENETIC BASIS OF CLINICALLY SUSPECTED ACHROMATOPSIA IN THE UNITED ARAB EMIRATES.

Achromatopsia (ACHM) is a genetically heterogenous relatively stationary congenital autosomal recessive cone disorder characterized typically by photophobia, low vision, nystagmus, hyperopia, grossly normal retinal appearance, and absent photopic responses by full-field electroretinography. Incomplete forms occur as well. This study investigates the genetic basis of clinically suspected ACHM in the United Arab Emirates. Retrospective case series (January 2016-December 2023) of patients with (1) clinically suspected ACHM or (2) mutations in ACHM-associated genes ( CNGA3 , CNGB3 , GNAT2 , PDE6C , PDE6H , AT6 ). Twenty-two clinically suspected patients (19 probands) were identified. Biallelic disease genes and the number of probands were CNGA3 (9), CNGB3 (6), PDE6C (1), GNAT2 (1), RGS9BP (1), and CNNM4 (1). Some mutant alleles were recurrent across different families. Two probands had their diagnoses revised after genetic testing and phenotypic reassessment to RGS9BP -related bradyopsia and CNNM4 -related Jalili syndrome. Three additional cases (making 22 total probands) were identified from ACHM gene mutation review-one each related to PDE6C , to AT6 , and to CNGB3 in concert with CNGA3 (triallelic disease). All three presented with macular discoloration, an atypical finding for classic ACHM. CNGA3 was the single most frequent implicated gene. Bradyopsia and Jalili syndrome can resemble incomplete ACHM. Recurrent mutant alleles may represent founder effects. Macular discoloration on presentation can occur in PDE6C -related disease, AT6 -related disease, and triallelic CNGB3 / CNGA3 -related disease. The possibility for triallelic disease exists and requires genetic counseling beyond that of simple autosomal recessive inheritance.

The Prevalence of Acute Compartment Syndrome in Pediatric Tibial Tubercle Fractures.

Tibial tubercle fractures are a unique class of pediatric orthopaedic injuries that frequently necessitate surgical treatment and strict monitoring due to the associated risk of acute compartment syndrome (ACS). However, current literature is conspicuously limited in its ability to estimate the risk of ACS after these fractures. Therefore, the purpose of this study is to utilize a nationwide database to estimate the prevalence of ACS after pediatric tibial tubercle fractures. We utilized the Healthcare Cost and Utilization Project's Kids' Inpatient Database (2019) to identify all pediatric patients, 18 years of age and under, with isolated tibial tubercle fractures (International Classification of Diseases, 10th revision Clinical Modification S82.151-S82.156) and ACS (T79.A0, T79.A2, T79.A29). Patients were excluded if they had additional lower extremity injuries (ie, tibial shaft, plateau, etc). A subanalysis was conducted for those undergoing fasciotomy, with and without an ACS diagnosis. Among the 591 isolated tibial tubercle fractures, there were 8 ACS cases for a prevalence of 1.35%. There were 22 (3.72%) additional cases of fasciotomy without an ACS diagnosis. All ACS cases were diagnosed during the original hospitalization; all were male and had closed fractures. The cohort included 469 teenagers (13+ years) and 77 pre-teens, with 40 females and 506 males. Racial demographics: 132 white, 232 black, 112 Hispanic, 15 Asian, 4 Native American, 23 unknown, and 28 others. No significant associations were found between ACS and age, race, insurance status, mechanism of injury, or hospital region. The rate of ACS in pediatric tibial tubercle fractures appears to be much lower than previously reported, at 1.35%. However, the nearly three-fold higher prevalence of fasciotomy without an ACS diagnosis, suggests a generous use of prophylactic fasciotomies and/or an undercharacterization of actual ACS cases from miscoding. This is the first and largest study to employ a nationally representative database to investigate the prevalence of ACS after tibial tubercle fractures. Level III.

Monitoring of atmospheric air quality in cities participating in the federal project “Clean Air” of the Far Eastern Economic Region

Introduction. Air pollution over 2021 was associated with about 6.7 thousand additional deaths and almost 1.1 million additional cases of illness among the Russian population. Conducting an atmospheric air quality assessment for the subsequent selection of priority measures aimed at reducing its negative impact on public health is the main task of the Clean Air federal project. The aim of the study is to assess the management of monitoring and air quality in the cities of Komsomolsk-on-Amur, Petrovsk-Zabaykalsky, and Ussuriysk before the implementation of the federal project “Clean Air”. Materials and methods. The monitoring programs for atmospheric air quality, the results of laboratory studies for 2021 were used. The number, location of observation posts, volumes, frequency of sampling, a list of indicators, the total number of samples, the number of samples exceeding the MPC, average annual, maximum one-time concentrations of pollutants were analyzed. Results. In Komsomolsk-on-Amur, atmospheric air quality monitoring was carried out at 4 stationary and 3 route posts, Ussuriysk – 1 mobile and 1 stationary post, Petrovsk-Zabaikalsky – 1 stationary post. All studied cities are characterized by systematic excesses of hygienic standards for specific indicators. The level of air pollution in the city of Komsomolsk-on-Amur is assessed as very high, in the cities of Ussuriysk and Petrovsk-Zabaikalsky – low. Despite the low level of air pollution, these towns are characterized by systematic excesses of hygienic standards of some indicators. Limitations. The study analyzed the management of monitoring and the results of laboratory studies of atmospheric air only in the cities of Komsomolsk-on-Amur, Ussuriysk, Petrovsk-Zabaykalsky. Conclusion. The existing monitoring system in the Ussuriysk, Komsomolsk-on-Amur and Petrovsk-Zabaykalsky cities fails to allow an objective assessing of the quality of atmospheric air and its impact on public health. To objective evaluation of the impact of atmospheric air quality on the health of the population of the studied cities, measures to optimize the monitoring system were proposed.

Phenotypic Expansion of Autosomal Dominant LZTR1-Related Disorders with Special Emphasis on Adult-Onset Features.

Leucine zipper-like transcription regulator 1 (LZTR1) acts as a negative factor that suppresses RAS function and MAPK signaling; mutations in this protein may dysregulate RAS ubiquitination and lead to impaired degradation of RAS superfamily proteins. Germline LZTR1 variants are reported in Noonan syndrome, either autosomal dominant or autosomal recessive, and in susceptibility to schwannomatosis. This article explores the genetic and phenotypic diversity of the autosomal dominant LZTR1-related disorders, compiling a cohort of previously published patients (51 with the Noonan phenotype and 123 with schwannomatosis) and presenting two additional adult-onset cases: a male with schwannomatosis and Parkinson's disease and a female with Noonan syndrome, generalized joint hypermobility, and breast cancer. This review confirms that autosomal dominant LZTR1-related disorders exhibit an extreme phenotypic variability, ranging from relatively mild manifestations to severe and multi-systemic involvement, and offers updated frequences of each clinical feature. The aim is to precisely define the clinical spectrum of LZTR1-related diseases, using also two new emblematic clinical cases. Gaining insight into the mechanisms underneath this variability is crucial to achieve precision diagnostics and the development of therapeutic interventions.

High Rates of Miscarriage and Stillbirth among Pregnant Women with Clade I Mpox (Monkeypox) Are Confirmed during 2023-2024 DR Congo Outbreak in South Kivu Province.

Mpox (monkeypox) is a neglected tropical disease that has received increased attention since the multi-nation outbreak that began in 2022. The virus is endemic in West and Central Africa, where the Democratic Republic of the Congo (DRC) is the most affected country. Clade I monkeypox virus (MPXV) infection is endemic in the DRC and has an overall case fatality rate of 10.6% among children and adults. A study conducted in Sankuru Province, DRC, from 2007 to 2011 demonstrated that 75% of pregnant women with mpox had miscarriages or stillbirth. Further analysis of a stillborn fetus showed that MPXV could infect both the placenta and fetus, causing congenital infection. No additional cases of Clade I MPXV in pregnant women were reported until a new outbreak occurred in South Kivu Province during 2023 and 2024. Eight pregnant women having Clade I MPXV infection were identified, of whom four had either miscarriages or stillbirth, representing a 50% fetal mortality rate. These reports confirm previous data from the DRC that indicate the capability of Clade I MPXV to affect the fetus, causing congenital infection and fetal loss in a high percentage of cases. In this article, we review both past and new data from the DRC on the effects of Clade I MPXV during pregnancy and discuss the association of mpox with fetal loss.

First report of Ug99 Wheat Stem Rust caused by Puccinia graminis f. sp. tritici in South Asia.

Since the emergence of Ug99 wheat stem rust in Uganda in 1998 (Pretorius et al. 2000), the threat of movement into South Asia has been a concern due to long-distance dispersal capacity of airborne spores (Brown and Hovmøller 2002; Singh et al. 2008; Meyer et al. 2017). Increased preparedness by comprehensive rust surveillance efforts and development and deployment of resistant cultivars in advance of an incursion into South Asia has been one of the success stories of the Borlaug Global Rust Initiative (Sharma et al. 2013). In November 2023, an off-season rust survey was conducted in Marpha, Gandaki and Bagmati provinces in Nepal. Rust was only observed at two sites, Dangdunge of Dolakha district and Mude of Sindhupalchok district, where spring wheat was grown as fodder crop outside the main cropping season. Rust infected wheat leaves (10-15 leaves per site) were air dried and sealed in envelopes that were shipped under permit to the Global Rust Reference Center, Denmark. Bulk samples of stem rust, Puccinia graminis f.sp. tritici (Pgt), were recovered from both envelopes, and single pustule isolates were raised and multiplied on Morocco and McNair. Meanwhile, specimens of dry leaves were subjected to SSR genotyping according to standard procedures (Patpour et al. 2022). One distinct multi-locus Pgt genotype was observed, identical to and representing 99% of Ug99 isolates within Clade I collected in East Africa between 2012-2022. A Pgt single pustule isolate from each of the sampling sites were inoculated onto 20 internationally agreed stem rust differential lines using standard procedures, and 14 supplementary lines providing additional resolution of pathogen virulence (Patpour et al. 2022). The pathotyping was repeated in two independent experiments, which resulted in the infection type pattern of Pgt race TTKTT (Supplementary Table 1). Additional independent SSR genotype assays of recovered isolates confirmed the prevalent genotype of Clade I (Patpour et al. 2022; Szabo et al. 2022). This first detection of Ug99 race TTKTT in South Asia emphasizes the need for continued coordinated international surveillance efforts and utilization of diverse sources of resistance to control stem rust in wheat. New surveillance efforts in Nepal during February-March 2024 did not reveal additional cases of wheat stem rust. However, more detailed and sustained rust surveillance efforts, assessment of the vulnerability of current wheat crops to Ug99 and other races of stem-, stripe/yellow- and leaf rust, as well as intensified breeding for rust resistance throughout the region is strongly recommended to meet current and future plant health risks.

MzIdentML 1.3.0 - Essential progress on the support of crosslinking and other identifications based on multiple spectra.

The mzIdentML data format, originally developed by the Proteomics Standards Initiative in 2011, is the open XML data standard for peptide and protein identification results coming from mass spectrometry. We present mzIdentML version 1.3.0, which introduces new functionality and support for additional use cases. First of all, a new mechanism for encoding identifications based on multiple spectra has been introduced. Furthermore, the main mzIdentML specification document can now be supplemented by extension documents which provide further guidance for encoding specific use cases for different proteomics subfields. One extension document has been added, covering additional use cases for the encoding of crosslinked peptide identifications. The ability to add extension documents facilitates keeping the mzIdentML standard up to date with advances in the proteomics field, without having to change the main specification document. The crosslinking extension document provides further explanation of the crosslinking use cases already supported in mzIdentML version 1.2.0, and provides support for encoding additional scenarios that are critical to reflect developments in the crosslinking field and facilitate its integration in structural biology. These are: (i) support for cleavable crosslinkers, (ii) support for internally linked peptides, (iii) support for noncovalently associated peptides, and (iv) improved support for encoding scores and the corresponding thresholds.

Human Case of Leptospirosis During a Canine Disease Outbreak - Wyoming, 2023.

Leptospirosis is a zoonotic bacterial disease spread through the urine of infected animals; the typical incubation period is 5-14 days. In approximately 90% of human cases, illness is asymptomatic or mild, characterized by fever, chills, myalgia, nausea, vomiting, diarrhea, headache, calf pain, and conjunctival suffusion, but severe illness can progress to multiorgan dysfunction and death. Although Wyoming is considered a low-risk area for leptospirosis because of its cold and semiarid climate, the Wyoming Department of Health was notified of a probable human case in August 2023, the first reported in the state since 1983. The patient had occupational exposure to dogs but did not report other risk factors. The same week that the human patient's illness began, public health authorities received notification of an increase in canine leptospirosis cases. Public health authorities investigated to determine potential sources of infection, identify additional cases, and recommend control measures. After public health outreach activities were implemented, canine vaccination practices changed substantially in the affected city: a survey conducted after the outbreak revealed that all responding veterinary clinics in the affected city were recommending the vaccine more frequently to dog owners and reporting higher levels of owner compliance with vaccination recommendations. Increased vaccination coverage offers protection from leptospirosis for both dogs and persons exposed to them. Leptospirosis should be considered in the differential diagnosis of persons with occupational exposure to animals and clinically compatible signs and symptoms, including fever, chills, myalgia, nausea, vomiting, diarrhea, headache, calf pain, and conjunctival suffusion, irrespective of geographic location.

Technological innovation, industry platforms or financialization? A comparative institutional perspective on Nokia, Apple, and Samsung

The puzzle of how Nokia lost the smartphone wars has intrigued recent scholarship. Despite Nokia’s dominant position in the mobile phone industry and its technological capabilities and reputation for strategic agility, it was completely wiped out from the market, only a few years after the launch of Apple’s iPhone. The article provides a comparative, historical and institutional account on the smartphone industry by focusing on three key players: Nokia, Apple, and Samsung. This perspective enriches earlier accounts that were overly focused on explaining Nokia’s decline by looking at internal organisational design and conflicts. We propose a two-pronged explanation focused on the reconfiguration of industry platforms and financialisation. The article suggests that single company histories could be enriched by integrating a comparative perspective that examines additional cases. We discuss opportunities for further research to understand how success or failure in technological innovation is embedded in a wider societal and institutional context.

Artificial intelligence and machine learning in peritoneal dialysis: a systematic review of clinical outcomes and predictive modeling.

The integration of artificial intelligence (AI) and machine learning (ML) in peritoneal dialysis (PD) presents transformative opportunities for optimizing treatment outcomes and informing clinical decision-making. This study aims to provide a comprehensive overview of the applications of AI/ML techniques in PD, focusing on their potential to predict clinical outcomes and enhance patient care. This systematic review was conducted according to PRISMA guidelines (2020), searching key databases for articles on AI and ML applications in PD. The inclusion criteria were stringent, ensuring the selection of high-quality studies. The search strategy comprised MeSH terms and keywords related to PD, AI, and ML. 793 articles were identified, with nine ultimately meeting the inclusion criteria. The review utilized a narrative synthesis approach to summarize findings due to anticipated study heterogeneity. Nine studies met the inclusion criteria. The studies varied in sample size and employed diverse AI and ML techniques, reflecting the breadth of data considered. Mortality prediction emerged as a recurrent theme, demonstrating the significance of AI and ML in prognostic accuracy. Predictive modeling extended to technique failure, hospital stay prediction, and pathogen-specific immune responses, showcasing the versatility of AI and ML applications in PD. This systematic review highlights the diverse applications of AI/ML in peritoneal dialysis, demonstrating their potential to enhance predictive accuracy, risk stratification, and decision support. However, limitations such as small sample sizes, single-center studies, and potential biases warrant further research and external validation. Future perspectives include integrating these AI/ML models into routine clinical practice and exploring additional use cases to improve patient outcomes and healthcare decision-making in PD.

Undifferentiated Round Cell Sarcoma With CRTC1::SS18 Fusion: Expanding Clinicopathologic Features of a Rare Translocation Sarcoma With Prominent Desmoplastic Stroma

Undifferentiated round cell sarcomas (URCS) represent a diverse group of tumors, including conventional Ewing sarcoma, round cell sarcoma with EWSR1/FUS–non-ETS fusions, CIC-rearranged sarcoma, and sarcoma with BCOR alterations. Since 2018, 3 cases of URCS with a novel CRTC1::SS18 gene fusion have been reported in the literature. Herein, we report 3 additional cases of CRTC1::SS18 sarcoma, thereby doubling the number of described cases and expanding the clinicopathologic features of this rare translocation sarcoma. Together with the previously reported cases, we show that the male-to-female ratio is 1:2 with a median age of 34 years (range, 12-42 years). Tumors occurred primarily in intramuscular locations involving the lower extremity. Histologically, all tumors contained uniform round-to-epithelioid cells with a moderate amount of eosinophilic cytoplasm growing in sheets and nests with prominent desmoplastic stroma reminiscent of desmoplastic small round cell tumor. Immunohistochemical results were nonspecific, demonstrating variable expression of CD99 (patchy), ALK, GATA3, and cyclin D1. RNA sequencing revealed CRTC1::SS18 gene fusions in all cases, involving exons 1 to 2 of CRTC1 (the 5′ partner gene) on chromosome 19 and either exon 2 or exon 4 of SS18 (the 3′ partner gene) on chromosome 18. The clinical course was variable. Although 1 previously reported case demonstrated aggressive behavior with a fatal outcome, 2 others had a relatively indolent course with gradual growth for 6 to 7 years prior to resection. Two cases developed metastatic disease, including 1 case with bilateral lung metastasis and 1 with locoregional spread to a lymph node. By analyzing the clinicopathologic features, we aimed to improve recognition of this rare translocation sarcoma to better understand its biologic potential, optimize patient management, and expand the current classification of URCS.

Using Scorecards to Tune Ethos Directive Templates: An Adaptive Radiation Therapy Individualized Approach-Cervix Dosimetric Planning Study

The Adaptive Radiation Therapy Individualized Approach-Cervix clinical trial uses predefined clinical directive templates (CDTs) combined with RapidPlan dose-volume histogram estimations (DVHe) to guide plan optimization in the Ethos treatment planning system. The dosimetric scorecard is a scoring tool that quantifies improvements in plan quality after physicians have precisely expressed their complete clinical intent. To our knowledge, this is the first study to use the dosimetric scorecard tool to tune an Ethos CDT to improve resulting plan quality. Iterative replanning was used to modify the draft CDT (CDT-1) in Ethos 1.1 to generate a new CDT (CDT-2) that maximized the clinical consensus scorecard's total score compared with CDT-1. CDT-2 was established, and resulting plans were compared with and without a DVHe. Additional fixed field intensity modulated radiation therapy beam geometries were compared between CDT-1 and CDT-2, both with DVHe. After obtaining favorable results when comparing CDT-1 versus CDT-2 for 2 test cases, 10 additional cases were retrospectively identified and tested. CDT-2 reduced organ at risk doses without compromising planning target volume coverage in the initial test cases. When combined with DVHe, CDT-2 marginally outperformed CDT-1. Plan quality further improved with a 19-field geometry. In the expanded analysis, CDT-2 achieved higher scores than CDT-1 in most cases, with the 19-field approach showing superiority. Optimization and calculation time increased by 1.9 minutes, monitor unit (MU)/field decreased by 44.4, whereas beam-on time increased by 2.8 minutes when increasing fields to 19 from 9. Reoptimization with Ethos 1.1 Maintenance Release 1 resulted in decreased MU and minimal score changes. The scorecard is an effective tool to adjust an Ethos CDT to improve the average calculated plan quality. It also allowed for easy evaluation of the dosimetric impact of other planning parameters (beam arrangements and use of DVHe) to identify the best approach. Using a finely tuned CDT is expected to improve planning efficiency and decrease intrainstitutional plan quality variability, benefiting cone beam computed tomography-guided adaptive radiation therapy.

Eight-Fold Increased COVID-19 Mortality in Autosomal Dominant Tubulointerstitial Kidney Disease due to MUC1 Mutations: An Observational Study.

MUC1 and UMOD pathogenic variants cause autosomal dominant tubulointerstitial kidney disease (ADTKD). MUC1 is expressed in kidney, nasal mucosa and respiratory tract, while UMOD is expressed only in kidney. Due to haplo-insufficiency ADTKD- MUC1 patients produce approximately 50% of normal mucin-1. To determine whether decreased mucin-1 production was associated with an increased COVID-19 risk, we sent a survey to members of an ADTKD registry in September 2021, after the initial, severe wave of COVID-19. We linked results to previously obtained ADTKD genotype and plasma CA15-3 (mucin-1) levels and created a longitudinal registry of COVID-19 related deaths. Surveys were emailed to 637 individuals, with responses from 89 ADTKD- MUC1 and 132 ADTKD- UMOD individuals. 19/83 (23%) ADTKD- MUC1 survey respondents reported a prior COVID-19 infection vs. 14/125 (11%) ADTKD- UMOD respondents (odds ratio (OR) 2.35 (95%CI 1.60-3.11, P = 0.0260). Including additional familial cases reported from survey respondents, 10/41 (24%) ADTKD- MUC1 individuals died of COVID-19 vs. 1/30 (3%) with ADTKD- UMOD , with OR 9.21 (95%CI 1.22-69.32), P = 0.03. The mean plasma mucin-1 level prior to infection in 14 infected and 27 uninfected ADTKD- MUC1 individuals was 7.06±4.12 vs. 10.21±4.02 U/mL ( P = 0.035). Over three years duration, our longitudinal registry identified 19 COVID-19 deaths in 360 ADTKD- MUC1 individuals (5%) vs. 3 deaths in 478 ADTKD- UMOD individuals (0.6%) ( P = 0.0007). Multivariate logistic regression revealed the following odds ratios (95% confidence interval) for COVID-19 deaths: ADTKD- MUC1 8.4 (2.9-29.5), kidney transplant 5.5 (1.6-9.1), body mass index (kg/m 2 ) 1.1 (1.0-1.2), age (y) 1.04 (1.0-1.1). Individuals with ADTKD- MUC1 are at an eight-fold increased risk of COVID-19 mortality vs. ADTKD- UMOD individuals. Haplo-insufficient production of mucin-1 may be responsible.