bluuebunny/crossref_metadata_2025 huggingface dataset:
Risk factors for the failure of first‐line PARP inhibitor maintenance therapy in patients with advanced ovarian cancer: Gynecologic Oncology Research Investigators Collaboration Study (GORILLA‐3004)
Authors: Kim Nam Kyeong , Kim Yeorae , Kim Hee Seung , Park Soo Jin , Hwang Dong Won , Lee Sung Jong , Yoo Ji Geun , Chang Suk‐Joon , Son Joo‐Hyuk , Kong Tae‐Wook , Kim Jeeyeon , Shim Seung‐Hyuk , Lee A Jin , Suh Dong Hoon , Lee Yoo‐Young
Published: September 2023

Objective

To identify the risk factors for failure of first‐line poly (ADP‐ribose) polymerase inhibitor (PARPi) maintenance therapy in patients with advanced ovarian cancer.

Method

Patients with stage III‐IV epithelial ovarian cancer who received first‐line PARPi maintenance therapy were retrospectively reviewed. Clinicopathologic factors were compared between two groups—recur/progression of disease (PD) and non‐recur/PD.

Results

In total, 191 patients were included. Median follow‐up was 9.9 months, and recurrence rate was 20.9%. BRCA mutations were found in 63.4% patients. Postoperative residual tumor (60.5% vs. 37.8%), non‐high grade serous carcinoma (HGSC) (15.0% vs. 6.0%), neoadjuvant chemotherapy (NAC) (55.0% vs. 35.8%), and pre‐PARPi serum CA‐125 levels ≥23.5 U/mL (35.9% vs. 15.2%) were more frequently observed in the recur/PD group. Multivariate Cox‐regression analysis revealed pre‐PARPi serum CA‐125 levels ≥23.5 U/mL (HR, 2.17; 95%CI, 1.03–4.57; p = 0.042), non‐HGSC (3.28; 1.20–8.97; p = 0.021), NAC (2.11; 1.04–4.26; p = 0.037), and no BRCA mutation (2.23; 1.12–4.44; p = 0.023) as independent risk factors associated with poor progression‐free survival (PFS). A subgroup analysis according to BRCA mutation status showed that pre‐PARPi serum CA‐125 levels ≥26.4 U/mL were the only independent risk factor for poor PFS in women with BRCA mutations (2.75; 1.03–7.39; p = 0.044). Non‐HGSC (5.05; 1.80–14.18; p = 0.002) and NAC (3.36; 1.25–9.04; p = 0.016) were independent risk factors in women without BRCA mutations.

Conclusion

High pre‐PARPi serum CA‐125 levels, non‐HGSC histology, NAC, and no BRCA mutation might be risk factors for early failure of first‐line PARPi maintenance therapy. In women with BRCA mutations, high pre‐PARPi serum CA‐125 levels, which represent a large tumor burden before PARPi, were the only independent risk factor for poor PFS.
Longitudinal associations among physical activity and sitting with endocrine symptoms and quality of life in breast cancer survivors: A latent growth curve analysis
Authors: Lucas Alexander R. , Kim Youngdeok , Lanoye Autumn , Franco R. Lee , Sutton Arnethea L. , LaRose Jessica G. , Ross Masey , Sheppard Vanessa B.
Published: September 2023

Purpose

Adjuvant endocrine therapy (AET) often causes debilitating endocrine symptoms that compromise quality of life (QOL) in women diagnosed with hormone receptor positive breast cancer (BC). We examined whether greater levels of physical activity (PA) or prolonged sitting were associated with reduced side effects or worse side effects of AET, respectively.

Methods

We used parallel process latent growth curve models to examine longitudinal patterns in PA and sitting behaviors, and their association with endocrine symptoms and QOL over 3 years of follow‐up in 554 female BC survivors undergoing AET.

Results

At baseline, women were a mean age of 59 years, mostly white (72%), with overweight/obesity (67%), and approximately 50% were within 1 year of diagnosis. Unconditional models showed significant increases in PA (p < 0.01) over time but no change in sitting. Endocrine symptoms, general and BC‐specific QOL all significantly worsened over time (p < 0.01). Parallel process models showed no cross‐sectional or longitudinal associations between PA and endocrine symptoms. Higher levels of baseline PA were associated with higher baseline QOL scores (p = 0.01) but changes in PA were not associated with changes in QOL. Conversely, more sitting at baseline was associated with worse endocrine symptoms, general and BC specific QOL (ps <0.01). At baseline, having better QOL scores was associated with increases in sitting (ps <0.01), while having worse endocrine symptoms was associated with a slower rate of increase in sitting (p < 0.01). Increases in sitting time were also associated with a slower rate of increase in endocrine symptoms (p = 0.017). Model fit statistics (x2, CFI, TLI, SRMR) were acceptable.

Conclusion

Both PA and sitting behaviors are important for the management of symptoms and in maintaining QOL in BC survivors. Women with already high symptom burden do not increase sitting time further but having better general and BC specific QOL to begin with means a greater decline over time.
Borderline Brenner tumor of the ovary with mucinous metaplasia: A case report
Authors: Shiravani Zahra , Bahrami Samaneh , Najib Fateme Sadat , Alavi Seyed Mohammad Amin
Published: September 2023

Key Clinical Message

To date, there have been disparate reports regarding borderline forms of Brenner tumors, while research on concomitant mucinous proliferation is even more irregular; however, it has been observed that proper diagnosis and treatment have proven to have a favorable prognosis on the aforementioned tumor.

Brenner tumor is a rare epithelial ovarian neoplasm responsible for 2%–3% of all ovarian tumors. These tumors are usually asymptomatic and can usually be found incidentally in pathological studies. They can also manifest themselves as abdominal pain or abnormal uterine bleeding. A 41‐year‐old female with a history of anemia referred to the hospital suffering from abdominal pain for at least 1 month before the referral period. Physical examination revealed a mobile palpable mass in the left lower abdomen. Ultrasound and pelvic computed tomography scan (CT scan) revealed a left ovarian complex cyst. Left salpingo‐oophorectomy was performed on the patient, and the cyst was removed. Pathological findings revealed an atypical proliferative Brenner tumor with mucinous metaplasia. To date, there have been disparate reports regarding borderline forms of Brenner tumors, while research on concomitant mucinous proliferation is even more irregular; however, it has been observed that proper diagnosis and treatment have proven to have a favorable prognosis on the aforementioned tumor.
Choriocarcinoma in tubal pregnancy: A case report
Authors: Najib Fateme Sadat , Bahrami Samaneh , Shiravani Zahra , Alavi Seyed Mohammad Amin
Published: September 2023

Key Clinical Message

Choriocarcinoma of the fallopian tube is extremely rare and highly susceptible to early metastasis. Clinical manifestations of ectopic pregnancy and choriocarcinoma are the same, and all patients with ectopic pregnancy should be evaluated for choriocarcinoma based on histopathological findings. Adjuvant chemotherapy (after surgery) is the proposed treatment for tubal choriocarcinoma.

Choriocarcinoma is a malignant epithelial tumor of the chorionic villi that often manifests after a normal or molar pregnancy. The primary tubal choriocarcinoma associated with ectopic pregnancy is extremely rare and can be misdiagnosed as an ectopic pregnancy since symptoms including vaginal bleeding, amenorrhea, elevated beta‐human chorionic gonadotropin (BHCG) levels, and pelvic pain are shared. A 34‐year‐old G4P3003 woman presented with a one‐week history of vaginal bleeding and right lower abdominal pain, which had intensified a day before admission. Clinical and paraclinical examinations pointed to a ruptured tubal pregnancy; hence, an emergency laparotomy was performed, and a right salpingectomy was carried out on the patient. However, a nonsignificant decline in BHCG level was observed, and histological examination revealed tubal choriocarcinoma; hence, a metastasis workup was carried out, yet no metastasis was detected. Six sessions of chemotherapy consisting of Etoposide, Methotrexate, Dactinomycin, Cyclophosphamide, and Vincristine (EMA‐CO) were administered without complication, in such a way that the BHCG level normalized after three sessions of chemotherapy. Evaluations after 1 year from the completion of chemotherapy revealed that the patient had no subsequent problems. Choriocarcinoma of the fallopian tube is extremely rare and highly susceptible to early metastasis. Clinical manifestations of ectopic pregnancy and choriocarcinoma are the same, and all patients with ectopic pregnancy should be evaluated for choriocarcinoma based on histopathological findings. Metastasis workup should be considered for all individuals with choriocarcinoma. Adjuvant chemotherapy (after surgery) is the proposed treatment for tubal choriocarcinoma.
Rare non‐trophoblastic vascular placental tumor: A diagnostic challenge
Authors: Limaiem Faten , Amor Anissa Ben , Saffar Khalil , Halouani Ahmed
Published: September 2023

Key Clinical Message

Pathologists should consider the differential diagnoses of placental chorioangioma, which encompass chorangiosis, chorangiomatosis, chorangiocarcinoma, intervillous thrombus, and placental infarct.

Chorioangiomas are rare non‐trophoblastic vascular neoplasms of the placenta, occurring in approximately 1% of pregnancies. Large chorioangiomas (>4 cm) are infrequent and associated with an increased risk of pregnancy complications. There are limited reports in the literature regarding uncomplicated cases of large placental chorioangiomas.
Elucidating the Effect of Nitrogen Occupancy on the Hydrogen Evolution Reaction for a Series of Titanium Oxynitride Electrocatalysts
Authors: Yang Guangmeimei , Zhou Yuxiang , Wang Mengnan , Murawski James , Oldham Louise I. , Tian Tian , Stephens Ifan E. L. , Kafizas. Andreas
Published: September 2023

Titanium nitride (TiN) shows desirable properties for use as an electrocatalyst and catalyst support, as it possesses high electrical conductivity and excellent corrosion resistance. However, the effect of oxygen content in the nitride lattice on its ability to drive the hydrogen evolution reaction (HER) is not well understood. Here, a series of titanium oxynitrides (TiNxO1‐x) with varied nitrogen occupancy (0.53≤x≤1.0) in the bulk have been fabricated by ammonolysis. Their specific activities towards the HER were normalised by the surface areas determined by BET and electrochemical methods. We show that the specific activities of these oxynitrides are strongly correlated with the bulk nitrogen occupancy, despite the similar surface composition derived from XPS analysis. Furthermore, a removal of the oxygen content in the bulk or at the surface was attributed to the upgraded performance (up to 25 % increase) seen during extended chronoamperometry (CA) tests. Our results show that minimising bulk oxygen content in this class of material is critical to achieve a more conductive and active material for the HER.
Oxidative Dehydrogenation of Propane over Supported Nickel Single‐Atom Catalyst†
Authors: Zhang Qian , Jiang Xunzhu , Li Yangyang , Tan Yuanlong , Jiang Qike , Liu Xiaoyan , Qiao Botao
Published: September 2023

Comprehensive Summary

Oxidative dehydrogenation of propane has been an ever‐growing field for propylene production due to its exothermic properties, of which overoxidation is the major drawback, with CO and even CO2 as undesired by‐products. For the purpose of getting higher propylene selectivity as well as yield, herein, we report Ni single atoms supported on calcium aluminate as an efficient catalyst candidate for propane oxidative dehydrogenation. Beneficial from higher valence states of Ni1 species, it shows 2—3 times as much propylene selectivity as that of Ni nanoparticles. About 14.2% C3H6 yield with 47.3% propylene selectivity has been achieved on Ni single atom catalyst and a good stability during 20 h test can be obtained as well.
Thixotropic Hydrogels Based on Laponite® and Cucurbituril for Delivery of Lipophilic Drug Molecules
Authors: Massaro Marina , Cinà Giuseppe , Borrego‐Sánchez Ana , Sainz‐Díaz C. Ignacio , Viseras‐Iborra César , Sánchez‐Espejo Rita , de Melo Barbosa Raquel , Leone Federica , Pibiri Ivana , Noto Renato , Riela Serena
Published: September 2023

Nowadays the use of hydrogels for biomedical purposes is increasing because of their interesting features that allow the development of targeted drug delivery systems. Herein, hydrogel based on Laponite® (Lap) clay mineral as gelator and cucurbit[6]uril (CB[6]) molecules were synthetized for the delivery of flufenamic acid (FFA) for potential topical application. Firstly, the interaction between CB[6] and FFA was assessed by UV‐vis spectroscopic measurements and molecular modeling calculations. Then, the obtained complex was used as filler for Lap hydrogel (Lap/CB[6]/FFA). The properties of the hydrogel in terms of viscosity and, self‐repair abilities were investigated; its morphology was imaged by scanning electron and polarized optical microscopies. Furthermore, the changes in the hydrodynamic radii and in the colloidal stability of CB[6]/Lap mixture were investigated in terms of translational diffusion from dynamic light scattering and ζ‐potential measurements. Finally, the kinetic in vitro release of FFA, from Lap/CB[6]/FFA hydrogel, was studied in a medium mimicking the pH of skin and the obtained results were discussed both by an experimental point of view and by molecular modeling calculations.
Analytical assay validation for acute myeloid leukemia measurable residual disease assessment by multiparametric flow cytometry
Authors: Tettero Jesse M. , Dakappagari Naveen , Heidinga Maaike E. , Oussoren‐Brockhoff Yvonne , Hanekamp Diana , Pahuja Anil , Burns Kerri , Kaur Pavinder , Alfonso Zeni , van der Velden Vincent H. J. , te Marvelde Jeroen G. , Hobo Willemijn , Slomp Jennichjen , Bachas Costa , Kelder Angele , Nguyen Kevin , Cloos Jacqueline
Published: September 2023

Background

Measurable residual disease (MRD) assessed by multiparametric flow cytometry (MFC) has gained importance in clinical decision‐making for acute myeloid leukemia (AML) patients. However, complying with the recent In Vitro Diagnostic Regulations (IVDR) in Europe and Food and Drug Administration (FDA) guidance in the United States requires rigorous validation prior to their use in investigational clinical trials and diagnostics. Validating AML MRD‐MFC assays poses challenges due to the unique underlying disease biology and paucity of patient specimens. In this study, we describe an experimental framework for validation that meets regulatory expectations.

Methods

Our validation efforts focused on evaluating assay accuracy, analytical specificity, analytical and functional sensitivity (limit of blank (LoB), detection (LLoD) and quantitation (LLoQ)), precision, linearity, sample/reagent stability and establishing the assay background frequencies.

Results

Correlation between different MFC methods was highly significant (r = 0.99 for %blasts and r = 0.93 for %LAIPs). The analysis of LAIP specificity accurately discriminated from negative control cells. The assay demonstrated a LoB of 0.03, LLoD of 0.04, and LLoQ of 0.1%. Precision experiments yielded highly reproducible results (Coefficient of Variation <20%). Stability experiments demonstrated reliable measurement of samples up to 96 h from collection. Furthermore, the reference range of LAIP frequencies in non‐AML patients was below 0.1%, ranging from 0.0% to 0.04%.

Conclusion

In this manuscript, we present the validation of an AML MFC‐MRD assay using BM/PB patient specimens, adhering to best practices. Our approach is expected to assist other laboratories in expediting their validation activities to fulfill recent health authority guidelines.
DBU Promoted Deformylative/Dehalogenative Difunctionalization to Access β‐Bromovinyl Aldehydes Derived from Tetralones**
Authors: Sau Madan , Dubey Sapana , Roy Shreya , Samanta Shubhankar , Das Tapas
Published: September 2023

Herein we have disclosed metal‐free 1,8‐diazabicyclo(5.4.0)undec‐7‐ene (DBU)‐catalyzed protocol for the deformylative/dehalogenative carbonylation and Michael addition of β‐bromovinyl aldehydes with acrylates and carbonylation followed by etherification with benzyl bromides to synthesize δ‐oxo esters and vinyl ethers respectively in good yields under an open atmosphere with broad substrate scope. Regeneration of starting material from vinyl ethers, organo‐catalytic and nucleophilic behavior of DBU is also discussed.
Biodiesel production through the transesterification of rapeseed oil over CaO‐MgO/SBA‐15 catalysts
Authors: Lazdovica Kristine , Kampars Valdis , Gaile Anastasija
Published: September 2023

Designing a cost‐effective and environmentally friendly heterogeneous catalyst for biodiesel production is essential. To achieve this, new 0.3‐CaO‐MgO/SBA‐15 and 0.8‐CaO‐MgO/SBA‐15 catalysts were prepared by the impregnation method. The new 0.3‐CaO‐MgO/SBA‐15 catalyst had higher purity, larger surface area, and pore volume than 0.8‐CaO‐MgO/SBA‐15, resulting in great catalytic activity for biodiesel production by transesterification of rapeseed oil with methanol. A biodiesel yield of 97.8 wt % was attained under the optimal reaction conditions of 5 wt % catalyst concentration, 15:1 methanol/oil molar ratio, 95°C reaction temperature, and reaction time of 4 h. Most of the parameters and properties of the obtained biodiesel correspond to the EN 14212 standard. The 0.3‐CaO‐MgO/SBA‐15 catalyst could be considered a potential candidate for biodiesel production on industrial level application attributed to intriguing properties like cost‐effectiveness, ease of synthesis, and environmental greenness.
Determination of the maximum run‐off sediment transport capacity during a rainstorm flood in a small watershed on the Loess Plateau
Authors: Wang Chenguang , Li Zhanbin , Wang Shanshan
Published: September 2023

The channel sediment transport capacity is an important parameter in soil erosion models, and it determines the proportion of soil erosion that is sent outside the watershed. However, the calculation and judgment methods for the sediment transport capacity of channel are still incomplete, and further research is needed. Therefore, this paper takes Chabagou, a typical watershed in the hilly and gully region of the Loess Plateau, as an example and, based on the measured hydrological and sediment data collected during rainstorm floods in 1961–1969 at three hydrological stations, Caoping, Shejiagou, and Tuanshangou, studies the sediment transport capacity of channels in a small watershed from the perspective of energy dissipation. Clearly, the sediment transport capacity is better determined by using a single flood and sediment concentration peak process. The discriminant conditions are determined for the sediment concentration to reach sediment transport capacity during the flood rising and falling sections of the sediment process of the small watershed storm flood. When determining sediment transport capacity based on the characteristics of the flood and sediment concentration peak, we find that sediment transport capacity is reached in the flood discharge peak when the flood discharge peak occurs earlier than the sediment concentration peak. When determining sediment transport capacity based on the flow discharge and sediment concentration characteristics of the sediment fall section, we find that when the flood event exhibits a counterclockwise hysteresis curve and a time‐lagged effect occurs, the sediment concentration at that time reaches sediment transport capacity. In this study, the sediment concentration as a function of run‐off amount is logarithmic at different subbasin scales when run‐off reaches its maximum capacity to transport sediment. The R2 is high, ranging from 0.78 to 0.92. The results of this research provide a reference for the study of sediment transport capacity.
HTTP header based phishing attack detection using machine learning
Authors: Shukla Sanjeev , Misra Manoj , Varshney Gaurav
Published: September 2023

In the past, many techniques like blacklisting/whitelisting, third‐party, search engine, visual similarity, heuristic, URL features, and website content were used for anti‐phishing. Search engine‐based, third‐party assisted tools and blacklist/whitelist fail to identify new phishing attacks resulting in high FPR. Heuristic and visual similarity approaches are slow, whereas URL and web content‐based techniques do not mimic the dynamic content of current websites and hence cannot stop zero‐day attacks. A study was conducted to understand the critical features used in the past for anti‐phishing, and we found 16 HTTP header features that were novel. In this paper, we have developed a real‐time, highly scalable, feature‐rich anti‐phishing detection technique based on ML that extracts the HTTP headers (predominantly security headers) from web pages to identify them as legitimate or phished. It is observed that phishing sites are short‐lived and are created to achieve a specific objective, like stealing the credential of a user. Once the goal is met, the sites are pulled down immediately. Hence these sites do not take pain to use the security features of web technology and only focus on making the site as similar as possible to the original website. Test results based on our novel features show high accuracy of 97.8% with an average response time of 1.57 s. We have created multiple datasets for different scenarios, like a dataset for website creation through phishing tools and a new dataset for testing unseen phishing attacks. The results thus obtained show detection accuracy of 99% and 95%, respectively.
Synthesis of {CB11} Monocarborane Sulfonamides by B2‐Selective Rhodium‐Catalyzed B−H Activation
Authors: Ye Zehua , Sun Jizeng , Jin Yujie , Lin Chuhao , Liu Jiyong , Duttwyler Simon
Published: September 2023

The synthesis of monocarborane sulfonamides is reported. The methodology relies on coupling of the anionic {CB11} boron cluster to sulfonyl azides. Under rhodium catalysis and with the assistance of a pyridine or pyrimidine directing group at the C1 position, the cluster undergoes B−H activation. Conditions have been identified that lead to B2‐selective mono‐sulfonamidation with concomitant loss of N2. The protocol requires no additional ligand, oxidant or base and enables B−N bond formation with various monocarborane and sulfonyl azide inputs. The new products possess the structure [1‐(heteroaryl)‐2‐(NHSO2Ar)−CB11H10]− and have been fully characterized by NMR spectroscopy and mass spectrometry. In addition, three solid state structures confirm the particular B2 substitution pattern. Furthermore, the stoichiometric reaction of the pyridinyl monocarborane precursor with Rh(III) affords a cyclometalated complex with a direct B−Rh bond that has also been characterized by X‐ray crystallography.
The Pharmacologic and Bacteriologic Properties of Oxazolidinones, a New Class of Synthetic Antimicrobials
Authors: Dresser Linda D. , Rybak Michael J.
Published: September 2023

The oxazolidinones are a new synthetic class of antimicrobials structurally unrelated to any agent presently marketed. Data pertaining to these compounds, with respect to their pharmacology, pharmacokinetics, pharmacodynamics, mechanism of action, and bacteriologic activity, focusing on the analogs linezolid (PNU 100766) and eperezolid (PNU 100592), were retrieved by MEDLINE search and review of relevant abstracts presented at recent clinical conferences. Since the drugs are still investigational, we obtained in vitro and animal data as well as available human studies. The oxazolidinones have bacteriostatic activity against a number of important pathogens including methicillin‐resistant Staphylococcus aureus, penicillin‐resistant Streptococcus pneumoniae, and vancomycin‐resistant enterococci. They appear to be efficacious and well tolerated both orally and parenterally. Their role remains to be elucidated by clinical trials.
Update on Clinical Antifungal Susceptibility Testing for Candida Species
Authors: Lewis Russell E. , Klepser Michael E. , Pfaller Michael A.
Published: September 2023

With the emergence of fungi as important nosocomial pathogens, increasing reports of antifungal resistance, and expanding drug therapy options, the need for clinically relevant antifungal susceptibility testing is evident. Over the last decade, the National Committee for Clinical Laboratory Standards (NCCLS) worked to standardize procedures for in vitro susceptibility testing of Candida species against fluconazole, itraconazole, 5‐fluorocytosine, and amphotericin B. With the establishment of a reproducible methodology, correlation of antifungal susceptibility in vitro with clinical outcome is a priority. The NCCLS proposed susceptibility breakpoints for the three agents against Candida species, with breakpoints for amphotericin B forthcoming. These breakpoints could provide useful guidance in some clinical situations involving azole or 5‐fluorocytosine therapy; however, routine susceptibility testing of fungal isolates should be discouraged.
Troglitazone in Type II Diabetes Mellitus
Authors: Sparano Nicole , Seaton Terry L.
Published: September 2023

Troglitazone, a new antihyperglycemic agent, is approved for use alone, with oral sulfonylureas, or with insulin in the treatment of type II diabetes mellitus. Rather than stimulating insulin secretion, it enhances insulin sensitivity. Potential advantages of troglitazone over oral sulfonylureas include decreased endogenous insulin concentrations, decreased exogenous insulin requirements, reduced hypoglycemic risk, and convenient once/day administration. The effect on morbidity and mortality from lowering endogenous and exogenous insulin concentrations remains to be determined. Troglitazone also has potential disadvantages. It induces cytochrome P450 isoenzyme 3A4, although few drug interactions have been identified to date. Serum transaminases must be monitored routinely because of rarely reported cases of idiosyncratic hepatocellular injury. In addition, the cost of troglitazone is much higher than that of other oral antihyperglycemic agents or insulin. Given the available information, troglitazone has limited benefit over oral sulfonylureas or metformin as monotherapy or in combination with oral sulfonylureas. Until additional combination and comparative studies have been done, the agent should be reserved for patients with poor glycemic control receiving high daily doses of insulin.
Antifungal Prophylaxis to Prevent Invasive Mycoses Among Bone Marrow Transplantation Recipients
Authors: Gubbins Paul O. , Bowman Jason L. , Penzak Scott R.
Published: September 2023

We reviewed the effect of systemic, intranasal, and lipid formulations of amphotericin B, fluconazole, itraconazole for antifungal prophylaxis. Specifically we reviewed the effect of antifungal prophylaxis on the development of fungal colonization, frequency of superficial and invasive mycosis, and overall mortality and that due to invasive mycoses in bone marrow transplantation recipients. A MEDLINE search was conducted to identify literature describing the risk factors, epidemiology, and chemoprophylaxis of invasive mycosis in these patients. Preliminary data published as abstracts at national infectious diseases and hematology conferences within the last 5 years were included. Antifungal prophylaxis reduces fungal colonization and superficial infection. The ability of antifungal prophylaxis to prevent systemic infection or reduce the need for empiric amphotericin B depends on specific variables. Ultimately, antifungal prophylaxis has no affect on overall mortality, and very little impact on mortality attributed to fungi.
Nitric Oxide Concentrations and Cerebrospinal Fluid Parameters in an Experimental Animal Model of Streptococcus pneumoniae Meningitis
Authors: Destache Christopher J. , Pakiz Catherine B. , Dash Alekha K. , Larsen Christine
Published: September 2023

Streptococcus pneumoniae is a common cause of meningitis. Nitric oxide (NO) has been implicated in causing cerebral edema. Modulating NO production in cerebrospinal fluid (CSF) may have a role in the treatment of bacterial meningitis. Experimental S. pneumoniae meningitis was induced in a rabbit model to determine CSF parameters and NO concentrations. An electrochemical probe in the CSF throughout the 7‐hour experiment monitored NO concentrations. The animals had S. pneumoniae (105) injected intracisternally and incubated for 1 hour. Cerebrospinal fluid 200–300 μl was obtained by intracisternal puncture at zero, 2, 4, and 7 hours after drug administration to measure glucose, protein, and lactic acid by standard chemical methods. White blood cell count was measured by hemocytometry. Three groups of five animals were used—control (C), ceftriaxone (CTX), and ceftriaxone plus dexamethasone (CTX+D). Ceftriaxone concentrations in CSF were obtained by microdialysis and analyzed by high‐performance liquid chromatography. Mean (± SEM) CSF white blood cell count was significantly higher at 2 hours in the C group than in the other two groups (C 7307 ± 1302, CTX 605 ± 345, CTX+D 730 ± 43/mm3, p<0.002). Ceftriaxone induced a significant rise in protein at 4 hours compared with the other groups (C 364 ± 107, CTX 1158 ± 797, CTX+D 365 ± 100 mg/dl, p<0.02). Cerebrospinal fluid lactic acid was significantly different at 4 and 7 hours between C and CTX+D groups (4‐hr C 8.0 ± 2.2, CTX+D 2.0 ± 0.4 mmol/L, p<0.05; 7‐hr C 10.2 ± 2.4, CTX+D 2.8 ± 0.8 mmol/L, p<0.01). Median NO concentrations were significantly elevated in the control group compared with the other two groups (C 11.7, CTX 6.8, CTX+D 6.5 μM, p<0.02 C vs CTX, p<0.01 C vs CTX+D). Average (± SEM) NO concentrations were significantly higher in the C group at 4 hours (18.1 ± 0.4, CTX 5.8 ± 1.8 μM, p<0.05; CTX+D 11.5 ± 4.0 μM, p>0.05), whereas they did not rise significantly until 7 hours in the CTX group (CTX 18.7 ± 0.7, C 8.9 ± 0.4 μM, p=0.055; CTX+D 8.1 ± 2.2 μM, p<0.05). These results indicate that ceftriaxone with or without dexamethasone significantly decreases lactic acid concentrations and white cell penetration into the CSF in an experimental model of S. pneumoniae meningitis. In addition, ceftriaxone induced a significant elevation in CSF protein. Median NO production in the CSF was significantly attenuated by ceftriaxone.
Caucasian versus African‐American Differences in Orosomucoid: Potential Implications for Therapy
Authors: McCollam Patrick L. , Crouch Michael A. , Arnaud Philippe
Published: September 2023

We conducted a prospective, nonrandomized study in healthy volunteers to determine if racial differences exist in orosomucoid (ORM) and its variants, and to examine quinidine and lidocaine binding to the protein. Total ORM serum concentrations were measured by Laurell‐Rocket immunoelectrophoresis. Allele types were determined by isoelectric focusing and immunoblotting. Total and unbound quinidine and lidocaine concentrations were measured with standard fluorescence polarization immunoassays after ultrafiltration. The frequency of the common ORM alleles was similar between 38 Caucasians and 67 African‐Americans. Mean total ORM concentration was significantly lower in Caucasians (57.3 ± 25.4 vs 73.2 ± 33.9 mg/dl, p=0.01). However, more Caucasians took oral contraceptives, which may have decreased ORM concentrations. Quinidine unbound fraction (UF) was related to ORM phenotype. The highest UF was found with ORM 1‐S (p=0.009). There were no significant relationships between ORM phenotype and lidocaine UF Overall, African‐Americans had higher ORM concentrations than Caucasians. Quinidine binding showed significant relationships to specific ORM variants.
Elevated Pancreatic Enzymes after Extended Propofol Therapy
Authors: Possidente Carl J. , Rogers Frederick B. , Osier Turner M. , Smith Thomas A.
Published: September 2023

Propofol is a sedative hypnotic agent often administered for intensive care sedation. A 28‐year‐old man who suffered a severe head injury developed elevated pancreatic enzymes after receiving extended high‐dosage propofol therapy. Amylase and lipase values gradually reduced toward normal after the drug was discontinued. Possible propofol‐induced pancreatitis was reported with short‐term but not with prolonged therapy. A definitive cause‐and‐effect relationship is unclear since head trauma also was reported to cause elevated pancreatic enzymes. Intensive care practitioners should be aware of this potential reaction.
Acute Renal Failure, Anterior Myocardial Infarction, and Atrial Fibrillation Complicating Epinephrine Abuse
Authors: Woodard Mark L. , Brent Lonnie D.
Published: September 2023

After injecting the solution extracted from a Primatene Mist inhaler, a patient experienced epinephrine overdose that resulted in an acute myocardial infarction and acute renal failure. The exact amount of epinephrine injected was unknown, but was thought to be between 82.5 and 124 mg, more than 25 times higher than the amount normally administered. Health care providers should be aware of this readily available source of epinephrine and the potential adverse effects associated with its inappropriate use.
Altered gut microbiome, bile acid composition and metabolome in sarcopenia in liver cirrhosis
Authors: Aliwa Benard , Horvath Angela , Traub Julia , Feldbacher Nicole , Habisch Hansjörg , Fauler Günter , Madl Tobias , Stadlbauer Vanessa
Published: September 2023

Background

Sarcopenia in liver cirrhosis is associated with low quality of life and high mortality risk. The pathogenesis has yet to be fully understood. We hypothesized that gut microbiome, bile acid (BA) composition and metabolites differ between cirrhotic patients with and without sarcopenia and contribute to pathogenesis.

Methods

Cirrhotic patients with (n = 78) and without (n = 38) sarcopenia and non‐cirrhotic controls with (n = 39) and without (n = 20) sarcopenia were included in this study. Faecal microbiome composition was studied by 16S rDNA sequencing, serum and faecal BA composition by ultra‐high‐performance liquid chromatography–tandem mass spectrometry, and metabolite composition in serum, faeces and urine by nuclear magnetic resonance.

Results

Bacteroides fragilis, Blautia marseille, Sutterella spp. and Veillonella parvula were associated with cirrhotic patients with sarcopenia, whereas Bacteroides ovatus was more abundant in cirrhotic patients without sarcopenia. We observed significantly elevated secondary BAs, deoxycholic acid (DCA; P = 0.01) and lithocholic acid (LCA; P = 0.02), and the ratios of deoxycholic acid to cholic acid (DCA:CA; P = 0.04), lithocholic acid to chenodeoxycholic acid (LCA:CDCA; P = 0.03) and 12 alpha‐hydroxylated to non‐12 alpha‐hydroxylated BAs (12‐α‐OH:non‐12‐α‐OH BAs; P = 0.04) in serum of cirrhotic patients with sarcopenia compared with cirrhotic patients without sarcopenia, indicating an enhanced transformation of primary to secondary BAs by the gut microbiome. CA (P = 0.02) and the ratios of CA:CDCA (P = 0.03) and total ursodeoxycholic acid to total secondary BAs (T‐UDCA:total‐sec‐BAs, P = 0.03) were significantly reduced in the stool of cirrhotic patients with sarcopenia compared with cirrhotic patients without sarcopenia. Also, valine and acetate were significantly reduced in the serum of cirrhotic patients with sarcopenia compared with cirrhotic patients without sarcopenia (P = 0.01 and P = 0.03, respectively). Multivariate logistic regression further confirmed the association of B. ovatus (P = 0.01, odds ratio [OR]: 12.8, 95% confidence interval [CI]: 168.1; 2.2), the ratios of 12‐α‐OH:non‐12‐α‐OH BAs (P = 0.03, OR: 2.54, 95% CI: 0.99; 6.55) and T‐UDCA:total‐sec‐BAs (P = 0.04, OR: 0.25, 95% CI: 0.06; 0.98) in serum and stool CA:CDCA (P = 0.04, OR: 0.79, 95% CI: 0.62; 0.99), and serum valine (P = 0.04, OR: 1.00, 95% CI: 1.02; 1.00) with sarcopenia in cirrhosis after correcting for the severity of liver disease and sex.

Conclusions

Our study suggests a potential functional gut microbiome–host interaction linking sarcopenia with the altered gut microbiomes, BA profiles and amino acids pointing towards a potential mechanistic interplay in understanding sarcopenia pathogenesis.
Simplified risk stratification in early cholecystectomy for acute cholecystitis based on age: A report from an institution with zero mortality
Authors: Matsui Yugo , Yao Siyuan , Ishikawa Kana , Homma Shusaku , Hosokawa Shinichi , Murakami Teppei , Kan Takatsugu , Nakajima Sanae , Harada Takehisa , Arii Shigeki
Published: September 2023

Background/Purpose

The existing risk stratification for early cholecystectomy in patients with acute cholecystitis (AC) is complex. This study aims to establish a simpler risk assessment for surgical complications after cholecystectomy based on age group.

Methods

This single‐center retrospective observational study enrolled 350 patients diagnosed with AC who underwent early cholecystectomy within 72 h of diagnosis from 2013 to 2021. Patients were divided into three subgroups based on age: young (<65 years), elderly (65–79 years), and very elderly (≥80 years). Since no mortality was observed, risk factors for the Clavien‐Dindo (CD) grade ≥ II complications were identified within the entire cohort and in each subgroup.

Results

There were 120 young, 130 elderly, and 100 very elderly patients. The overall prevalence of complications with CD grade ≥ II was 11.1%. Age and Tokyo Guidelines 18 (TG18) severity were independent risk factors for surgical complications in the whole cohort. Subgroup analysis revealed that there was no independent risk factor in the young group. Meanwhile, age and poor physical status were independent risk factors in the elderly group, and TG18 severity in the very elderly group.

Conclusion

Evaluation of only age, physical status, and TG18 severity may be sufficient for risk stratification of surgical complications of AC.
Computed Tomography–Measured Psoas Density Predicts Outcomes After Enterocutaneous Fistula Repair
Authors: Lo Wilson D. , Evans David C. , Yoo Taehwan
Published: September 2023

Background

Low muscle mass and quality are associated with poor surgical outcomes. We evaluated computed tomography (CT)–measured psoas muscle density as a marker of muscle quality and physiologic reserve and hypothesized that it predicts poor outcomes after enterocutaneous fistula repair (ECF).

Methods

We conducted a retrospective cohort study of patients 18–90 years old with ECF who failed nonoperative management, requiring elective operative repair at The Ohio State University (2005–2016), and who received preoperative abdomen/pelvis CT scan with intravenous contrast within 3 months of the operation. Psoas Hounsfield unit average calculations were measured at the L3 level. One‐year leak rate, mortality (90 days, 1 years, and 3 years), complication risk, length of stay, dependent discharge, and 30‐day readmission were compared with Hounsfield unit average calculation (HUAC).

Results

One hundred patients met inclusion criteria. Patients were stratified into interquartile ranges based on HUAC. The lowest HUAC interquartile was our low muscle quality (LMQ) cutoff, which was associated with 1‐year leak (relative risk [RR] = 2.10, P < .005), 1‐year mortality (RR = 2.22, P < .04) and 3‐year mortality (RR = 2.13, P < .007), complication risk (RR = 1.54, P < .001), and dependent discharge (RR = 2.50, P < .004) compared to patients without LMQ.

Conclusions

Psoas muscle density is a significant predictor of poor outcomes in ECF repair. This readily available measure of physiologic reserve can identify patients with ECF who have increased risk and may benefit from additional interventions and recovery time before operative repair.
Effects of release method on the survival, somatic growth, and body condition of headstarted turtles
Authors: Wijewardena Tharusha , Mandrak Nicholas E. , Paterson James E. , Davy Christina M. , Edge Christopher B. , Lentini Andrew M. , Litzgus Jacqueline D.
Published: September 2023

Headstarting involves ex situ rearing of vulnerable life stages, then releasing individuals into the wild once they are larger and less vulnerable to predation. Sometimes, headstarted animals display underdeveloped behaviors that may lead to an acclimation period of reduced survival and growth after release. Using data from a 6‐year headstarting program, we tested whether the early release condition affected survival, body condition, and somatic growth rate in 2 groups of headstarted Blanding's turtles (Emydoidea blandingii) released into Rouge National Urban Park (RNUP) in Toronto, Ontario, Canada. The first group included turtles released directly into the wild (i.e., hard release). The second group included turtles released into an in situ enclosure in which individuals remained for a week without food supplementation before being fully released into the wild (i.e., delayed release). Release condition did not affect survival or growth rate. In the delayed‐release group, body condition initially declined rapidly and remained low for up to 1 year after release. Given the lack of wild juveniles in RNUP, we compared body condition of headstarted turtles at various time points since release to similar‐sized wild juveniles from 2 other Ontario populations, one from Algonquin Provincial Park (APP) and one near Lake Erie (LE). Body condition of headstarted turtles was similar to those of wild APP turtles regardless of release method, and higher than those of wild LE turtles. Our results indicate that delayed release did not improve post‐release outcomes for headstarted turtles in an urban landscape and headstarted turtles sustain similar health metrics as wild turtles.
Treatment Modality Impact on Patient‐Reported Quality of Life in Human Papilloma Virus‐Associated Oropharyngeal Carcinoma
Authors: Plonowska‐Hirschfeld Karolina A. , Gulati Arushi , Stephens Erika M. , Ochoa Edgar , Xu Mary Jue , Ha Patrick K. , Heaton Chase M. , Yom Sue S. , Chan Jason W. , Algazi Alain , Kang Hyunseok , Ryan William R.
Published: September 2023

Objective

To prospectively compare the impact of treatment modality on patient‐reported quality of life (QOL) in human papillomavirus‐associated oropharynx squamous cell carcinoma (HPV + OPSCC).

Study Design

Prospective cohort study.

Setting

Academic medical center.

Methods

One hundred one patients with American Joint Committee on Cancer (AJCC) 8th edition T1‐3 N0‐2 HPV + OPSCC completed the European Organization for Research and Treatment of Cancer Quality of Life Core questionnaire and Head and Neck Module pretreatment and 3‐month and 1‐year posttreatment. Mean score changes were compared to published minimal clinically important differences.

Results

Patients underwent surgery alone (SA: N = 42, 42%), surgery with adjuvant radiation (S‐RT: N = 10, 10%), surgery with adjuvant chemoradiation (S‐CRT: N = 8, 8%), definitive radiation (RT: N = 11, 11%), or definitive chemoradiation (CRT: N = 30, 30%). SA, S‐[C]RT, and [C]RT patients all reported clinically significant difficulty with sense of taste/smell persisting at 1 year. S‐[C]RT and [C]RT patients reported statistically and clinically significant worse salivary dysfunction and problems with social eating at 1 year than SA. S‐[C]RT patients reported statistically and clinically significant worse fatigue and head and neck pain compared to [C]RT and SA patients at 3 months, but normalized at 1 year. S‐CRT compared to S‐RT had statistically and clinically worse physical and role functioning and swallowing difficulties at 3 months but this difference was resolved by 1‐year posttreatment.

Conclusion

HPV + OPSCC patients after SA report the lowest posttreatment QOL impact, whereas after S‐CRT report the highest symptom burden. Careful selection for definitive surgery is important given the possibility of adjuvant CRT. Patients can experience persistent sense taste and smell difficulties at 1 year with all treatment modalities.

Level of Evidence

3 Laryngoscope, 134:1687–1695, 2024
Variables Affecting Cochlear Implant Performance After Loss of Residual Hearing
Authors: Thompson Nicholas J. , Dillon Margaret T. , Nix Evan P. , Overton Andrea B. , Selleck A. Morgan , Dedmon Matthew M. , Brown Kevin D.
Published: September 2023

Objective

Determine variables that influence post‐activation performance for cochlear implant (CI) recipients who lost low‐frequency acoustic hearing.

Methods

A retrospective review evaluated CNC word recognition for adults with normal to moderately severe low‐frequency hearing (preoperative unaided thresholds of ≤70 dB HL at 250 Hz) who were implanted between 2012 and 2021 at a tertiary academic center, lost functional acoustic hearing, and were fit with a CI‐alone device. Performance scores were queried from the 1, 3, 6, 12, and 24‐month post‐activation visits. A linear mixed model evaluated the effects of age at implantation, array length (long vs. mid/short), and preoperative low‐frequency hearing (normal to mild, moderate, and moderately severe) on speech recognition with a CI alone.

Results

113 patients met the inclusion criteria. There was a significant main effect of interval (p < 0.001), indicating improved word recognition post‐activation despite loss of residual hearing. There were significant main effects of age (p = 0.029) and array length (p = 0.038), with no effect of preoperative low‐frequency hearing (p = 0.171). There was a significant 2‐way interaction between age and array length (p = 0.018), indicating that older adults with mid/short arrays performed more poorly than younger adults with long lateral wall arrays when functional acoustic hearing was lost.

Conclusion

CI recipients with preoperative functional low‐frequency hearing experience a significant improvement in speech recognition with a CI alone as compared to preoperative performance—despite the loss of low‐frequency hearing. Age and electrode array length may play a role in post‐activation performance. These data have implications for the preoperative counseling and device selection for hearing preservation candidates.

Level of Evidence

4 Laryngoscope, 134:1868–1873, 2024
Denitrification and the challenge of scaling microsite knowledge to the globe
Authors: Robertson G. Philip
Published: September 2023

Our knowledge of microbial processes—who is responsible for what, the rates at which they occur, and the substrates consumed and products produced—is imperfect for many if not most taxa, but even less is known about how microsite processes scale to the ecosystem and thence the globe. In both natural and managed environments, scaling links fundamental knowledge to application and also allows for global assessments of the importance of microbial processes. But rarely is scaling straightforward: More often than not, process rates in situ are distributed in a highly skewed fashion, under the influence of multiple interacting controls, and thus often difficult to sample, quantify, and predict. To date, quantitative models of many important processes fail to capture daily, seasonal, and annual fluxes with the precision needed to effect meaningful management outcomes. Nitrogen cycle processes are a case in point, and denitrification is a prime example. Statistical models based on machine learning can improve predictability and identify the best environmental predictors but are—by themselves—insufficient for revealing process‐level knowledge gaps or predicting outcomes under novel environmental conditions. Hybrid models that incorporate well‐calibrated process models as predictors for machine learning algorithms can provide both improved understanding and more reliable forecasts under environmental conditions not yet experienced. Incorporating trait‐based models into such efforts promises to improve predictions and understanding still further, but much more development is needed.
Boundary controllability for a degenerate beam equation
Authors: Camasta Alessandro , Fragnelli Genni
Published: September 2023

The paper deals with the controllability of a degenerate beam equation. In particular, we assume that the left end of the beam is fixed, while a suitable control acts on the right end of it. As a first step, we prove the existence of a solution for the homogeneous problem, then we prove some estimates on its energy. Thanks to them, we prove an observability inequality, and using the notion of solution by transposition, we prove that the initial problem is null controllable.