Prevalence of cervical intraepithelial lesions and associated factors among women attending a cervical cancer clinic in Western Uganda; results based on Pap smear cytology.

Introduction: There are high incidence and mortality rates of cervical cancer among females in East Africa. This is exacerbated by limited up-to-date data on premalignant lesions and associated factors in this setting. In this study, we determined the prevalence of cervical intraepithelial lesions and associated factors among women attending the Mbarara Regional Referral Hospital cervical cancer clinic in Southwestern Uganda. Methods: In this cross-sectional study, 364 participants were recruited from among women attending the Mbarara Regional Referral Hospital cervical cancer clinic from 1 April to 30 June 2023. On consent, the study nurse collected demographic data and Pap smears, which were microscopically examined and reported by a laboratory scientist and a pathologist following the Bethesda grading system (2014). Statistical analyses were done in STATA version 17, using proportions, Chi-square, bivariate, and multivariate logistic regression analysis to determine associated factors at ⩽0.05 significance level. Results: The mean age of participants was 41.9 years. A third of all study participants (37.6%, 132/351) were contraceptive users, mostly hormonal contraceptives (87.1%, 115/132). Almost 88% (307/351) had an unknown Human Papilloma Virus status. The prevalence of cervical intraepithelial lesions among our study participants was 6.6% (23/351), of which 73.9% (17/23) were low-grade squamous intraepithelial lesions. More than half (9/17, 52.9%) of low-grade squamous intraepithelial lesions were active hormonal contraceptive users. Use of hormonal contraceptives (OR: 3.032, p: 0.0253), use of intrauterine devices (OR: 6.284, p: 0.039), and any family history of cervical cancer (OR: 4.144, p: 0.049) were significantly associated with cervical intraepithelial lesions. Conclusion: The prevalence of cervical intraepithelial lesions was 6.6%, lower than global estimates. Use of hormonal and intrauterine device contraceptives, as well as family history of cervical cancer, were significantly associated with cervical intraepithelial lesions among our study population. Prospective studies are recommended to further understand associations between different types of intrauterine devices and hormonal contraceptives, and cervical lesions.

Potential strategic allocation of nuptial gift proteins of the neotropical katydid Conocephalus ictus (Orthoptera Tettigoniidae).

In many katydids, the male feeds his mate with a large gelatinous spermatophore. While providing large spermatophores can increase female fecundity and lifespan, it may also decrease their sexual receptivity, benefiting male fitness. Allocating resources to these edible gifts may entail a lower apportionment of them to other functions, generating a trade-off between somatic and reproductive functions. Despite their effect on male and female fitness, little is known of the compounds associated with katydid spermatophores. Our study found 177 different putative proteins in the spermatophore of Conocephalus ictus, with no correlation between male body size with spermatophore mass, number, concentration and mass of proteins. However, we did observe a negative relationship between male forewing length and protein concentration, and a negative relationship between the mass of the spermatophore transferred to the females and their body size, suggesting a resource allocation trade-off in males, but also strategic transference of resources based on female quality.

Phase 1b study of mirvetuximab soravtansine, a folate receptor alpha (FRα)-targeting antibody-drug conjugate, in combination with carboplatin and bevacizumab in patients with platinum-sensitive ovarian cancer.

OBJECTIVE: Evaluate the antitumor activity and safety profile of the triplet combination of mirvetuximab soravtansine (MIRV), carboplatin, and bevacizumab in recurrent, platinum-sensitive ovarian cancer. METHODS: Participants with recurrent, platinum-sensitive epithelial ovarian, fallopian tube, or primary peritoneal cancer (1-2 prior lines of therapy) received MIRV (6 mg/kg adjusted ideal body weight), carboplatin (AUC5), and bevacizumab (15 mg/kg) once every 3 weeks. Carboplatin could be discontinued after 6 cycles per investigator discretion; continuation of MIRV+bevacizumab as maintenance therapy was permitted. Eligibility included folate receptor alpha (FRα) expression by immunohistochemistry (≥50% of cells with ≥2+ intensity; PS2+ scoring); prior bevacizumab was allowed. Tumor response, duration of response (DOR), progression-free survival (PFS), and adverse events (AEs) were assessed. RESULTS: Forty-one participants received triplet therapy, with a median of 6, 12, and 13 cycles of carboplatin, MIRV, and bevacizumab, respectively. The confirmed objective response rate was 83% (9 complete and 25 partial responses). The median DOR was 10.9 months; median PFS was 13.5 months. AEs (any grade) occurred as expected, based on each agent's safety profile; most common were diarrhea (83%), nausea (76%), fatigue (73%), thrombocytopenia (71%), and blurred vision (68%). Most cases were mild to moderate (grade ≤2), except for thrombocytopenia, for which most drug-related discontinuations occurred, and neutropenia. CONCLUSIONS: This triplet regimen (MIRV+carboplatin+bevacizumab) was highly active, with a tolerable AE profile in participants with recurrent, platinum-sensitive, FRα-expressing ovarian cancer. Thrombocytopenia was the primary cause of dose modifications. These outcomes compare favorably to historical data reported for platinum-based chemotherapy plus bevacizumab regimens in similar patient populations.

A Trip Back Home: Resistance to Herbivores of Native and Non-Native Plant Populations of Datura stramonium.

When colonizing new ranges, plant populations may benefit from the absence of the checks imposed by the enemies, herbivores, and pathogens that regulated their numbers in their original range. Therefore, rates of plant damage or infestation by natural enemies are expected to be lower in the new range. Exposing both non-native and native plant populations in the native range, where native herbivores are present, can be used to test whether resistance mechanisms have diverged between populations. Datura stramonium is native to the Americas but widely distributed in Spain, where populations show lower herbivore damage than populations in the native range. We established experiments in two localities in the native range (Mexico), exposing two native and two non-native D. stramonium populations to natural herbivores. Plant performance differed between the localities, as did the abundance of the main specialist herbivore, Lema daturaphila. In Teotihuacán, where L. daturaphila is common, native plants had significantly more adult beetles and herbivore damage than non-native plants. The degree of infestation by the specialist seed predator Trichobaris soror differed among populations and between sites, but the native Ticumán population always had the lowest level of infestation. The Ticumán population also had the highest concentration of the alkaloid scopolamine. Scopolamine was negatively related to the number of eggs deposited by L. daturaphila in Teotihuacán. There was among-family variation in herbivore damage (resistance), alkaloid content (scopolamine), and infestation by L. daturaphila and T. soror, indicating genetic variation and potential for further evolution. Although native and non-native D. stramonium populations have not yet diverged in plant resistance/constitutive defense, the differences between ranges (and the two experimental sites) in the type and abundance of herbivores suggest that further research is needed on the role of resource availability and adaptive plasticity, specialized metabolites (induced, constitutive), and the relationship between genealogical origin and plant defense in both ranges.

Understanding the pathogenic mechanisms and therapeutic effects in neurocysticercosis.

Despite being a leading cause of acquired seizures in endemic regions, the pathological mechanisms of neurocysticercosis are still poorly understood. This study aims to investigate the impact of anthelmintic treatment on neuropathological features in a rat model of neurocysticercosis. Rats were intracranially infected with Taenia solium oncospheres and treated with albendazole + praziquantel (ABZ), oxfendazole + praziquantel (OXF), or untreated placebo (UT) for 7 days. Following the last dose of treatment, brain tissues were evaluated at 24 h and 2 months. We performed neuropathological assessment for cyst damage, perilesional brain inflammation, presence of axonal spheroids, and spongy changes. Both treatments showed comparable efficacy in cyst damage and inflammation. The presence of spongy change correlated with spheroids counts and were not affected by anthelmintic treatment. Compared to white matter, gray matter showed greater spongy change (91.7% vs. 21.4%, p < 0.0001), higher spheroids count (45.2 vs. 0.2, p = 0.0001), and increased inflammation (72.0% vs. 21.4%, p = 0.003). In this rat model, anthelmintic treatment destroyed brain parasitic cysts at the cost of local inflammation similar to what is described in human neurocysticercosis. Axonal spheroids and spongy changes as markers of damage were topographically correlated, and not affected by anthelmintic treatment.

Insularization drives physiological condition of Amazonian dung beetles.

The fragmentation and degradation of otherwise continuous natural landscapes pose serious threats to the health of animal populations, consequently impairing their fitness and survival. While most fragmentation ecology studies focus on habitat remnants embedded withinn terrestrial matrices, the effects of true insularization remains poorly understood. Land-bridge islands created by major dams leads to habitat loss and fragmentation, negatively affecting terrestrial biodiversity. To assess the effects of insularization, we conducted a study on the key aspects of dung beetle physiological condition and body size throughout the Balbina Hydroelectric Reservoir located in the Central Amazon. We assessed these traits at the population and assemblage levels, collecting dung beetles from both forest islands and continuous forest areas while analyzing various landscape variables. We show that landscapes with higher forest cover positively affected dung beetle body size. Interestingly, dung beetle responses to insularization were species-dependent; larger islands tended to host larger individuals of Deltochilum aspericole, while in Canthon triangularis, smaller islands showed larger body sizes. However, individuals from the mainland were larger than those from the islands. Moreover, the proportion of closed-canopy forest in the landscapes also impacted physiological attributes. It negatively affected the body size of Deltochilum aspericole and the lipid mass of Dichotomius boreus, but positively affected the lipid mass of Canthon triangularis. These findings contribute to a better understanding of how habitat fragmentation in aquatic matrices affects the size structure and physiology of insect assemblages. This is essential in formulating effective conservation strategies for preserving biodiversity loss in tropical forest regions and mitigating the consequences of hydropower infrastructure.

Tocotrienols Provide Radioprotection to Multiple Organ Systems through Complementary Mechanisms of Antioxidant and Signaling Effects.

Tocotrienols have powerful radioprotective properties in multiple organ systems and are promising candidates for development as clinically effective radiation countermeasures. To facilitate their development as clinical radiation countermeasures, it is crucial to understand the mechanisms behind their powerful multi-organ radioprotective properties. In this context, their antioxidant effects are recognized for directly preventing oxidative damage to cellular biomolecules from ionizing radiation. However, there is a growing body of evidence indicating that the radioprotective mechanism of action for tocotrienols extends beyond their antioxidant properties. This raises a new pharmacological paradigm that tocotrienols are uniquely efficacious radioprotectors due to a synergistic combination of antioxidant and other signaling effects. In this review, we have covered the wide range of multi-organ radioprotective effects observed for tocotrienols and the mechanisms underlying it. These radioprotective effects for tocotrienols can be characterized as (1) direct cytoprotective effects, characteristic of the classic antioxidant properties, and (2) other effects that modulate a wide array of critical signaling factors involved in radiation injury.

The conversion of native savannah into pasturelands does not affect exclusively species diversity: Effects on physiological condition of a highly abundant dung beetle species.

Dung beetles are efficient indicators to obtain responses regarding the effects of land use change on biodiversity. Although the biological consequences of Cerrado conversion into pasture have been observed at the assemblage scale, there are no cues regarding the effects of tropical savanna conversion into pasture on physiological condition of dung beetle individuals. In this study, we evaluated whether native and non-native habitats in Cerrado affect the physiological condition and body traits of males and females of Phanaeus palaeno. The individuals were collected from a Cerrado fragment (sensu stricto) and an exotic pasture (Urochloa spp.). Physiological condition was assessed through the estimation of individuals' dry body mass, fat mass, and muscle mass. Body traits were estimated through individual body size and males' horn length. We did not find differences between dung beetle morphological traits between Cerrado and pastures. However, individuals collected in exotic pastures had lower dry mass and fat mass, but higher muscle mass, than in conserved Cerrado. Understanding how the land use change affects individuals' body condition is essential to maintain abundant and healthy populations of dung beetles in human-modified landscapes. Although the estimation of physiological condition is logistically more complex than species body traits, future studies aiming to present complex and finer ecological responses of dung beetles should incorporate physiological data to their approaches.

The Liquid Biopsy Consortium: Challenges and opportunities for early cancer detection and monitoring.

The emerging field of liquid biopsy stands at the forefront of novel diagnostic strategies for cancer and other diseases. Liquid biopsy allows minimally invasive molecular characterization of cancers for diagnosis, patient stratification to therapy, and longitudinal monitoring. Liquid biopsy strategies include detection and monitoring of circulating tumor cells, cell-free DNA, and extracellular vesicles. In this review, we address the current understanding and the role of existing liquid-biopsy-based modalities in cancer diagnostics and monitoring. We specifically focus on the technical and clinical challenges associated with liquid biopsy and biomarker development being addressed by the Liquid Biopsy Consortium, established through the National Cancer Institute. The Liquid Biopsy Consortium has developed new methods/assays and validated existing methods/technologies to capture and characterize tumor-derived circulating cargo, as well as addressed existing challenges and provided recommendations for advancing biomarker assays.

Extrinsic and intrinsic preanalytical variables affecting liquid biopsy in cancer.

Liquid biopsy, through isolation and analysis of disease-specific analytes, has evolved as a promising tool for safe and minimally invasive diagnosis and monitoring of tumors. It also has tremendous utility as a companion diagnostic allowing detection of biomarkers in a range of cancers (lung, breast, colon, ovarian, brain). However, clinical implementation and validation remains a challenge. Among other stages of development, preanalytical variables are critical in influencing the downstream cellular and molecular analysis of different analytes. Although considerable progress has been made to address these challenges, a comprehensive assessment of the impact on diagnostic parameters and consensus on standardized and optimized protocols is still lacking. Here, we summarize and critically evaluate key variables in the preanalytical stage, including study population selection, choice of biofluid, sample handling and collection, processing, and storage. There is an unmet need to develop and implement comprehensive preanalytical guidelines on the optimal practices and methodologies.

Inaugurating High-Throughput Profiling of Extracellular Vesicles for Earlier Ovarian Cancer Detection.

Detecting early cancer through liquid biopsy is challenging due to the lack of specific biomarkers for early lesions and potentially low levels of these markers. The current study systematically develops an extracellular-vesicle (EV)-based test for early detection, specifically focusing on high-grade serous ovarian carcinoma (HGSOC). The marker selection is based on emerging insights into HGSOC pathogenesis, notably that it arises from precursor lesions within the fallopian tube. This work thus establishes murine fallopian tube (mFT) cells with oncogenic mutations and performs proteomic analyses on mFT-derived EVs. The identified markers are then evaluated with an orthotopic HGSOC animal model. In serially-drawn blood of tumor-bearing mice, mFT-EV markers increase with tumor initiation, supporting their potential use in early cancer detection. A pilot clinical study (n = 51) further narrows EV markers to five candidates, EpCAM, CD24, VCAN, HE4, and TNC. The combined expression of these markers distinguishes HGSOC from non-cancer with 89% sensitivity and 93% specificity. The same markers are also effective in classifying three groups (non-cancer, early-stage HGSOC, and late-stage HGSOC). The developed approach, for the first time inaugurated in fallopian tube-derived EVs, could be a minimally invasive tool to monitor women at high risk of ovarian cancer for timely intervention.

Impaired spatial working memory and reduced hippocampal neuronal density in a rat model of neurocysticercosis.

Neurocysticercosis (NCC) is the most common parasitic disease affecting the nervous system and is a leading cause of acquired epilepsy worldwide, as well as cognitive impairment, especially affecting memory. The aim of this study was to evaluate the effect of NCC on spatial working memory and its correlation with hippocampal neuronal density, in a rat model of NCC. This experimental study was conducted on female (n = 60) and male (n = 73) Holtzman rats. NCC was induced by intracranial inoculation of T. solium oncospheres in 14 day-old-rats. Spatial working memory was assessed using the T-maze test at 3, 6, 9, and 12 months post-inoculation, and sensorimotor evaluation was performed at 12 months post-inoculation. Hippocampal neuronal density was evaluated by immunostaining of NeuN-positive cells of the CA1 region. Of the rats inoculated with T. solium oncospheres, 87.2% (82/94) developed NCC. The study showed a significant decline in spatial working memory over a 1-year follow-up period in rats experimentally infected with NCC. Males showed an early decline that started at 3 months, while females demonstrated it at 9 months. Additionally, a decrease in neuronal density was observed in the hippocampus of NCC-infected rats, with a more significant reduction in rats with cysts in the hippocampus than in rats with cysts in other brain areas and control rats. This rat model of NCC provides valuable support for the relationship between neurocysticercosis and spatial working memory deficits. Further investigations are required to determine the mechanisms involved in cognitive impairment and establish the basis for future treatments.

CRISPR/Cas13a-Based MicroRNA Detection in Tumor-Derived Extracellular Vesicles.

MicroRNAs (miRNAs) in extracellular vesicles (EVs) play essential roles in cancer initiation and progression. Quantitative measurements of EV miRNAs are critical for cancer diagnosis and longitudinal monitoring. Traditional PCR-based methods, however, require multi-step procedures and remain as bulk analysis. Here, the authors introduce an amplification-free and extraction-free EV miRNA detection method using a CRISPR/Cas13a sensing system. CRISPR/Cas13a sensing components are encapsulated in liposomes and delivered them into EVs through liposome-EV fusion. This allows for accurately quantify specific miRNA-positive EV counts using 1 × 108  EVs. The authors show that miR-21-5p-positive EV counts are in the range of 2%-10% in ovarian cancer EVs, which is significantly higher than the positive EV counts from the benign cells (<0.65%). The result show an excellent correlation between bulk analysis with the gold-standard method, RT-qPCR. The authors also demonstrate multiplexed protein-miRNA analysis in tumor-derived EVs by capturing EpCAM-positive EVs and quantifying miR-21-5p-positive ones in the subpopulation, which show significantly higher counts in the plasma of cancer patients than healthy controls. The developed EV miRNA sensing system provides the specific miRNA detection method in intact EVs without RNA extraction and opens up the possibility of multiplexed single EV analysis for protein and RNA markers.

Electrokinetically enhanced label-free plasmonic sensing for rapid detection of tumor-derived extracellular vesicles.

ANALYSIS: of rare circulating extracellular vesicles (EV) from early cancers or different types of host cells requires extremely sensitive EV sensing technologies. Nanoplasmonic EV sensing technologies have demonstrated good analytical performances, but their sensitivity is often limited by EVs' diffusion to the active sensor surface for specific target EV capture. Here, we developed an advanced plasmonic EV platform with electrokinetically enhanced yields (KeyPLEX). The KeyPLEX system effectively overcomes diffusion-limited reactions with applied electroosmosis and dielectrophoresis forces. These forces bring EVs toward the sensor surface and concentrate them in specific areas. Using the keyPLEX, we showed significant improvements in detection sensitivity by ∼100-fold, leading to the sensitive detection of rare cancer EVs from human plasma samples in 10 min. The keyPLEX system could become a valuable tool for point-of-care rapid EV analysis.

Trends in the use of neoadjuvant chemotherapy for low-grade serous ovarian cancer in the United States.

OBJECTIVE: To describe trends in neoadjuvant chemotherapy (NACT) use for low-grade serous ovarian carcinoma (LGSOC) and to quantify associations between NACT and extent of cytoreductive surgery. METHODS: We identified women treated for stage III or IV serous ovarian cancer in a Commission on Cancer accredited program between January 2004-December 2020. Regression models were developed to evaluate trends in NACT use for LGSOC, to identify factors associated with receipt of NACT, and to quantify associations between NACT and bowel or urinary resection at the time of surgery. Demographic and clinical factors were used for confounder control. RESULTS: We observed 3350 patients who received treatment for LGSOC during the study period. The proportion of patients who received NACT increased from 9.5% in 2004 to 25.9% in 2020, corresponding to an annual percent change of 7.2% (95% CI 5.6-8.9). Increasing age (rate ratio (RR) 1.15; 95% CI 1.07-1.24), and stage IV disease (RR 2.66; 95% CI 2.31-3.07) were associated with a higher likelihood of receiving NACT. For patients with high-grade disease, NACT was associated with a decrease in likelihood of bowel or urinary surgery (35.3% versus 23.9%; RR 0.68, 95% CI 0.65-0.71). For LGSOC, NACT was associated with a higher likelihood of these procedures (26.6% versus 32.2%; RR 1.24, 95% CI 1.08-1.42). CONCLUSION: NACT use among patients with LGSOC has increased from 2004 to 2020. While NACT was associated with a lower rate of gastrointestinal and urinary surgery among patients with high-grade disease, patients with LGSOC receiving NACT were more likely to undergo these procedures.

Prevalence, risk factors and evolution of diabetes mellitus after treatment in primary aldosteronism. Results from the SPAIN-ALDO registry.

PURPOSE: To evaluate the prevalence, risk factors and evolution of diabetes mellitus (DM) after targeted treatment in patients with primary aldosteronism (PA). METHODS: A retrospective multicenter study of PA patients in follow-up at 27 Spanish tertiary hospitals (SPAIN-ALDO Register). RESULTS: Overall, 646 patients with PA were included. At diagnosis, 21.2% (n = 137) had DM and 67% of them had HbA1c levels < 7%. In multivariate analysis, family history of DM (OR 4.00 [1.68-9.53]), the coexistence of dyslipidemia (OR 3.57 [1.51-8.43]) and advanced age (OR 1.04 per year of increase [1.00-1.09]) were identified as independent predictive factors of DM. Diabetic patients were on beta blockers (46.7% (n = 64) vs. 27.5% (n = 140), P < 0.001) and diuretics (51.1% (n = 70) vs. 33.2% (n = 169), p < 0.001) more frequently than non-diabetics. After a median follow-up of 22 months [IQR 7.5-63.0], 6.9% of patients developed DM, with no difference between those undergoing adrenalectomy and those treated medically (HR 1.07 [0.49-2.36], p = 0.866). There was also no significant difference in the evolution of glycemic control between DM patients who underwent surgery and those medically treated (p > 0.05). CONCLUSION: DM affects about one quarter of patients with PA and the risk factors for its development are common to those of the general population. Medical and surgical treatment provides similar benefit in glycemic control in patients with PA and DM.

Incidence of vascular lesions associated with disruption of the bile duct secondary to cholecystectomy.

BACKGROUND: One of the most serious complications of cholecystectomy is bile duct disruption, which can be associated with concomitant vascular injury in up to 3.4%. The incidence, demographic characteristics and treatment are underreported worldwide. OBJECTIVE: To determine the incidence of vascular lesions in patients with a diagnosis of bile duct disruption secondary to cholecystectomy from January 1, 2015 to December 31, 2019, confirmed by preoperative CT angiography or intraoperative findings. METHOD: Retrospective, observational and analytical study of a series of cases between 2015 and 2019. Where a total of 144 cases of bile duct disruption were found, 15 cases (10%) with concomitant vascular injury. RESULTS: The most frequent vascular injury was of the right hepatic artery in 13 patients (87%). The level of biliary disruption most frequently associated was Strasberg E3 and E4 in 5 patients (36%), respectively. The treatment of vascular injury was ligation of the injured vessel in 11 patients (73%). The treatment established for the repair of biliary disruption was the hepatic jejunum anastomosis in 14 patients (93%). CONCLUSIONS: The presence of injury at the level of the right hepatic artery is the most frequent and its ligation did not show a significant impact on biliodigestive reconstruction, as long as an adequate technique is performed (Hepp-Couinaud).

ANTECEDENTES: Una de las complicaciones más serias de la colecistectomía es la disrupción de la vía biliar, la cual puede estar asociada con lesión vascular concomitante hasta en un 3.4%. Su incidencia, características demográficas y tratamiento son infrarreportados en todo el mundo. OBJETIVO: Conocer la incidencia de las lesiones vasculares en pacientes con diagnóstico de disrupción de la vía biliar secundaria a colecistectomía, del 1 de enero de 2015 al 31 de diciembre de 2019, confirmado por angiotomografía preoperatoria o por hallazgos transoperatorios. MÉTODO: Estudio retrospectivo, observacional y analítico de una serie de casos del 2015 al 2019. Encontrando 144 casos de disrupción de la vía biliar, 15 (10%) con lesión vascular concomitante. RESULTADOS: La lesión vascular más frecuente fue la de arteria hepática derecha, en 13 pacientes (87%). El nivel de disrupción biliar más habitualmente asociado fue Strasberg E3 y E4, en 5 pacientes (36%) cada uno. El tratamiento de la lesión vascular fue ligadura del vaso en 11 pacientes (73%). El tratamiento de la disrupción de vía biliar fue anastomosis hepático-yeyunal en 14 pacientes (93%). CONCLUSIONES: La presencia de lesión de la arteria hepática derecha es la más frecuente y su ligadura no tiene una repercusión significativa en la reconstrucción biliodigestiva, siempre y cuando se realice una técnica adecuada (Hepp-Couinaud).

Kidney function in patients with ovarian cancer treated with poly (ADP-ribose) polymerase (PARP) inhibitors.

BACKGROUND: Poly (ADP-ribose) polymerase inhibitors (PARPi) have revolutionized the treatment of ovarian cancer; however, real-world data on kidney function among patients treated with PARPi are lacking. METHODS: We identified adults treated with olaparib or niraparib between 2015 and 2021 at a major cancer center in Boston, MA, USA. We determined the incidence of any acute kidney injury (AKI), defined as at least a 1.5-fold rise in serum creatinine from baseline in the first 12 months following PARPi initiation. We calculated the percentage of patients with any AKI and sustained AKI and adjudicated the etiologies by manual chart review. We compared trajectories in estimated glomerular filtration rate (eGFR) among PARPi-treated and carboplatin and paclitaxel-treated patients with ovarian cancer, matched by baseline eGFR. RESULTS: Of 269 patients, 60 (22.3%) developed AKI, including 43 of 194 (22.1%) olaparib-treated patients and 17 of 75 (22.7%) niraparib-treated patients. Only 9 of 269 (3.3%) had AKI attributable to the PARPi. Of the 60 patients with AKI, 21 (35%) had sustained AKI, of whom 6 had AKI attributable to the PARPi (2.2% of the whole cohort). eGFR declined within 30 days post-PARPi initiation by 9.61 (SD = 11.017) mL/min per 1.73 m2 but recovered by 8.39 (SD = 14.05) mL/min per 1.73 m2 within 90 days after therapy cessation. There was no difference in eGFR at 12 months post-therapy initiation in patients receiving PARPi or controls receiving carboplatin and paclitaxel (P = .29). CONCLUSIONS: AKI is common following PARPi initiation as is a transient decline in eGFR; however, sustained AKI directly attributable to the PARPi and long-term eGFR decline are uncommon.

Neurosurgery Morbidity and Mortality: A Prospective Surgical and Medical Analysis.

OBJECTIVE: The analysis of morbidity and mortality is fundamental for improving the quality of patient care. The objective of this study was to evaluate the combined medical and surgical morbidity and mortality of neurosurgical patients. METHODS: We performed a daily prospective compilation of morbidities and mortalities during a consecutive 4-month period in all the patients who were 18 years of age or older and had been admitted to the neurosurgery service at the Puerto Rico Medical Center. For each patient, any surgical or medical complication, adverse event, or death within 30 days was included. The patients' comorbidities were analyzed for their influence on mortality. RESULTS: Fifty-seven percent of the patients presented at least 1 complication. The most frequent complications were hypertensive episodes, mechanical ventilation for more than 48 hours, sodium disturbances, and bronchopneumonia. Twenty-one patients died, for an overall 30-day mortality of 8.2%. Mechanical ventilation for more than 48 hours, sodium disturbances, bronchopneumonia, unplanned intubation, acute kidney injury, blood transfusion, shock, urinary tract infection, cardiac arrest, arrhythmia, bacteremia, ventriculitis, sepsis, elevated intracranial pressure, vasospasm, stroke, and hydrocephalus were significant factors for mortality. None of the analyzed patients' comorbidities were significant for mortality or longer length of stay. The type of surgical procedure did not influence the length of stay. CONCLUSION: The mortality and morbidity analysis provided valuable neurosurgical information that may influence future treatment management and corrective recommendations. Indication and judgment errors were significantly associated with mortality. In our study, the patients' comorbidities were not significant for mortality or increased length of stay.

Risk exposure factors influencing the frequency of road crashes during the COVID-19 pandemic in Ciudad Juarez, Mexico. A negative binomial spatial regression model.

The article aims to investigate the influence of risk exposure factors on the frequency of road crashes from January to August 2020 in Ciudad Juarez, Mexico. It is a longitudinal study with four data sets: road crashes, population and housing census, location of economic activities, and road network information. Specifically, this study investigates the relationship between exposure factors - demographics, main roads and land use - and road crashes. A mixed method analysis was employed, (1) spatial analysis using GIS techniques; and (2) a negative binomial spatial regression model. The results showed a strong spatial dependence (0.274; p-value 0.00) of road crashes in the census tracts, and this effect was statistically significant (0.007) in the spatial regression model. In the model, a high probability (<0.05) of road crashes in the census tracts was found with the population aged 15 to 65 years, the length of main roads and the level of road coverage (Engel index), land uses with economic activities of an industrial and commercial character. The findings of this study successfully capture the social, economic, and urban conditions during the January-August 2020 period in the context of the COVID-19 pandemic. This new knowledge could help create preventive plans and policies to address the frequency of road crashes.