Obstetric and neonatal outcomes, antiseizure medication profile, and seizure types in pregnant women in a vulnerability state from Brazil.

This retrospective cohort study described the obstetric and neonatal outcomes, antiseizure medication (ASM) use, and types of seizures in pregnant women with epilepsy (PWWE). Data collected from the medical records of 224 PWWE aged < 40 years with controlled or refractory seizures and 492 pregnant women without epilepsy (PWNE) control group from high-risk maternity hospitals in Alagoas between 2008 and 2021 were included in this study. The obstetric and neonatal outcomes observed in PWWE were pregnancy-related hypertension (PrH) (18.4%), oligohydramnios (10.3%), stillbirth (6.4%), vaginal bleeding (6%), preeclampsia (4.7%), and polyhydramnios (3%). There was a greater likelihood of PrH in PWWE with generalized tonic-clonic seizures (GTCS) and that of maternal intensive care unit (ICU) admissions in those with GTCS and status epilepticus, and phenytoin and lamotrigine use. PWWE with GTCS had a higher risk of stillbirth and premature delivery. PWWE with status epilepticus were treated with lamotrigine. Phenobarbital (PB) with diazepam were commonly used in GTCS and status epilepticus. Total 14% patients did not use ASM, while 50.2% used monotherapy and 35.8% used polytherapy. Total 60.9% of patients used PB and 25.2% used carbamazepine. This study described the association between the adverse obstetric and neonatal outcomes and severe seizure types in PWWE.

Precision medicine for urothelial carcinoma: An international perspective.

The treatment landscape of urothelial cancers has evolved in the last decade with the approval of chemotherapy, immune checkpoint inhibitors, targeted therapies, and antibody drug conjugates. Although improvements in response and survival have been achieved with these strategies, in some scenarios their benefit is still questionable. Current efforts to identify prognostic and predictive biomarkers are crucial for better patient selection and treatment outcomes. In this paper we will review the most promising biomarkers under investigation, such as molecular classifiers, genomic alterations, programmed cell death ligand 1 expression, tumor mutational burden, circulating tumor DNA, urinary biomarkers among others, for muscle invasive bladder cancer and metastatic urothelial cancers. Deeper understanding of these biomarkers will aid clinical decision-making and help tailor treatment strategies.

Tracking and considerations on the therapeutic management of neuropathic pain in adult patients with sickle cell disease / Rastreamento e considerações sobre a conduta terapêutica na dor neuropática em pacientes adultos com doença falciforme

ABSTRACT BACKGROUND AND OBJECTIVES: Sickle cell disease is considered the most common hereditary disorder in Brazil. The chronic pain resulting from some complications of sickle cell disease is still poorly understood, inadequately described, and under-researched. This study aimed to characterize chronic pain in individuals with sickle cell disease, evaluate its treatment, and discuss the importance of studying it as a distinct pathology. METHODS: A cross-sectional study based on comparative analysis between two associations of sickle cell disease patients, one in Brazil and the other in France. The Pain Detect Questionnaire was used to assess neuropathic pain, and Odds Ratio was used to evaluate the strength of the association between opioid use and the recurrence of chronic painful crises. RESULTS: In Brazil, the Pain Detect questionnaire revealed that 55% of patients had a probable neuropathic component, 23% negative, and 22% uncertain. In France, the application resulted in 51% for probable presence, 29% for negative, and 20% for uncertain. All patients reported constant pain. As for the frequent use of opioids, the results were 62% in Brazil and 32% in France. The Odds Ratio calculation results were: OR 15.14 (95% CI = 4.777- 41.4, p < 0.0001) in Brazil; and OR 7.5 (95% CI = 2.121- 25.74, p = 0.0013) in France. CONCLUSION: While it is commonly believed that pain in sickle cell disease is primarily related to somatic and visceral tissue damage after vaso-occlusive events, this study indicated emerging evidence of neuropathic processes involved. Thus, there should be a significant concern about the management of chronic pain and particularly opioid dependence in Brazil.

RESUMO JUSTIFICATIVA E OBJETIVOS: Dentre as alterações hereditárias, a doença falciforme é considerada a mais comum no Brasil. A dor crônica decorrente de suas complicações ainda é mal compreendida, inadequadamente descrita e pouco pesquisada. O presente estudo teve como finalidade caracterizar a dor crônica em indivíduos com doença falciforme, avaliar o seu tratamento e discutir a importância de seu estudo como uma doença em si. METODOS: Estudo transversal, baseado na análise comparativa entre duas associações de indivíduos acometidos pela doença falciforme, com sede no Brasil e na França. Foi aplicado o questionário Pain Detect para avaliação da dor neuropática e a Odds Ratio para avaliar a intensidade de associação entre o uso de opioides e a recorrência de crises álgicas de cunho crônico. RESULTADOS: O questionário Pain Detect apontou que no Brasil 55% de pacientes da doença calciforme apresentam componente neuropático provável, 23% negativo e 22% incerto. Na França, os resultaram foram de 51% para componente provável, 29% negativo e 20% incerto. Dos acometidos pela doença, 100% relataram dores constantes, sendo que fizeram uso frequente de opioides 62% no Brasil e 32% na França. O cálculo do Odds Ratio apontou os seguintes resultados: OR 15,14 (IC 95% = 4,777- 41,4, p < 0,0001) no Brasil; e OR 7,5 (IC 95% = 2,121- 25,74, p = 0,0013) na França. CONCLUSÃO: Embora haja uma crença de que a dor na doença falciforme seja primariamente relacionada à lesão tecidual a nível somático e visceral após os eventos vasoclusivos, o estudo apontou evidências emergentes de processos neuropáticos envolvidos. Assim, deve haver uma preocupação quanto ao manejo da dor crônica e em especial à dependência química pelos opioides no Brasil.

Evaluating Immune-Related Adverse Events Using PRO-CTCAE in a Phase II Study of Ipilimumab for Hormone-Sensitive Prostate Cancer.

Introduction: Use of the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) during chemotherapy is associated with decreased hospitalization rates, improved quality of life, and longer survival. Limited data exist on the benefit of this symptom assessment tool for monitoring immune-related adverse events (irAEs). Methods: We incorporated irAE-related items from the National Cancer Institute's (NCI) PRO-CTCAE in a trial evaluating ipilimumab in combination with androgen deprivation therapy in 16 patients with hormone-sensitive prostate cancer. For comparison, NCI's CTCAE version 4.0 was used by clinicians. Results: IrAE-related PRO-CTCAE surveys and matched CTCAEs (184 pairs) reporting abdominal pain, diarrhea, fatigue, anorexia, nausea, vomiting, rash, and pruritus were collected at each treatment administration and during follow-up. Fatigue, diarrhea, rash, and pruritus were the symptoms most frequently reported by both patients and clinicians. Agreement was lowest for pruritus (κ = 0.10) and highest for rash (κ = 0.64). IrAEs were more commonly reported and of higher grade with PRO-CTCAE scores compared with CTCAE grades. Conclusion: PRO-CTCAEs focused on irAEs capture the patient's immunotherapy experience while complementing the clinician's toxicity assessment measures. Further study is needed to assess PRO-CTCAE's utility in identifying and managing irAEs.

Universal method for the isolation of microvessels from frozen brain tissue: A proof-of-concept multiomic investigation of the neurovasculature.

The neurovascular unit, comprised of vascular cell types that collectively regulate cerebral blood flow to meet the needs of coupled neurons, is paramount for the proper function of the central nervous system. The neurovascular unit gatekeeps blood-brain barrier properties, which experiences impairment in several central nervous system diseases associated with neuroinflammation and contributes to pathogenesis. To better understand function and dysfunction at the neurovascular unit and how it may confer inflammatory processes within the brain, isolation and characterization of the neurovascular unit is needed. Here, we describe a singular, standardized protocol to enrich and isolate microvessels from archived snap-frozen human and frozen mouse cerebral cortex using mechanical homogenization and centrifugation-separation that preserves the structural integrity and multicellular composition of microvessel fragments. For the first time, microvessels are isolated from postmortem ventromedial prefrontal cortex tissue and are comprehensively investigated as a structural unit using both RNA sequencing and Liquid Chromatography with tandem mass spectrometry (LC-MS/MS). Both the transcriptome and proteome are obtained and compared, demonstrating that the isolated brain microvessel is a robust model for the NVU and can be used to generate highly informative datasets in both physiological and disease contexts.

Elucidating the Mechanisms of Pulsed Radiofrequency for Pain Treatment.

Pulsed radiofrequency is a well-documented treatment option for multiple painful conditions where pulses of energy are delivered close to neural elements. Since its earliest adoption, this technique has gained increasing acceptance as a minimally invasive procedure, and new applications are evolving. Studies have shown microscopic and biochemical changes that reflect beneficial effects; however, the exact mechanism of action is not yet completely understood. To redress this paucity, 11,476 articles of scientific relevance published between 1980 and November 2022 were mined through a search of the PubMed database, arriving at 49 studies both in animals and humans. In general, the experimental studies examined have shown that pulsed radiofrequency induces multiple changes with antinociceptive and neuromodulatory effects. These modifications include changes in neural and glial cells, synaptic transmission, and perineural space. Studies also reveal that pulsed radiofrequency regulates inflammatory responses, cellular signaling proteins, and the expression of genes related to pain transmission, acting in biological processes in structures such as myelin, mitochondria, axons, glial cells, connective tissue, regulation of proteins, ion channels, and neurotransmitters.

Correlation between the event of the COVID-19 pandemic and symptoms of anxiety, depression and temporomandibular disorder in university students: cross-sectional study / Correlação entre o evento da pandemia de COVID-19 e sintomas de ansiedade, depressão e de disfunção temporomandibular em estudantes universitários: estudo transversal

ABSTRACT BACKGROUND AND OBJECTIVES: The COVID-19 pandemic has been shown to be a probable aggravator of psychological responses such as anxiety and depression. This study aimed to assess the correlation between symptoms of anxiety and depression during the COVID-19 pandemic and the existence of symptoms associated with temporomandibular dysfunction (TMD) in a Brazilian university population. METHODS: This epidemiological, cross-sectional clinical study evaluated its variables of interest using the COVID-19 Fear Scale, Hospital Anxiety and Depression Scale (HADS-A and HADS-D), Diagnostic Criteria for Temporomandibular Dysfunction (DC/TMD) and Oral Behavior Checklist (OBC) questionnaires. RESULTS: A total of 373 participants (females = 273) with a mean age of 23.8±5.45 years were included in this study. In addition, 78.2% of participants with anxiety symptoms and 54.5% of participants with depression symptoms reported a high level of TMD-related parafunction (p<0.01). The presence of anxiety symptoms increased the odds of developing intense fear of COVID-19 by 14.9 times (p<0.001) and the odds of developing moderate fear of COVID-19 by 3.5 times (p<0.001). The presence of an intense fear of COVID-19 increased the chances of developing anxiety symptoms by 17.15 times (p<0.001), while the presence of a moderate fear increased these chances by 3.12 times (p<0.001). In addition, the presence of intense (p=0.01) or moderate (p=0.018) COVID-19 fears increased the odds of developing TMD-related pain symptoms by 2.47 and 1.84 times, respectively, in this population. CONCLUSION: The presence of painful TMD symptoms was possibly influenced by fear of COVID-19. This, in turn, was related to the presence of anxiety and depression symptoms reported by the target population of this study.

RESUMO JUSTIFICATIVA E OBJETIVOS: A pandemia de COVID-19 mostrou-se um provável agravante de respostas psicológicas como ansiedade e depressão. Este estudo teve como objetivo avaliar a correlação entre sintomas de ansiedade e depressão durante o período da pandemia de COVID-19 e a existência de sintomas associados à disfunção temporomandibular (DTM) em uma população universitária brasileira. MÉTODOS: Este estudo clínico epidemiológico e transversal avaliou as suas variáveis de interesse por meio dos questionários Escala de Medo do COVID-19, Escala Hospitalar de Ansiedade e Depressão (HADS-A e HADS-D), Critérios Diagnósticos para Disfunção Temporomandibular (DC/DTM) e Checklist de Comportamentos Orais (OBC). RESULTADOS: Ao todo, 373 participantes (sexo feminino = 273), com média de idade de 23,8±5,45 anos foram incluídos neste estudo. Ademais, 78,2% dos participantes com sintomas de ansiedade e 54,5% dos participantes com sintomas de depressão reportaram alto nível de parafunção relacionada à DTM (p<0,01). A presença de sintomas de ansiedade aumentou em 14,9 vezes as chances de desenvolvimento de um quadro de medo intenso do COVID-19 (p<0,001) e de um quadro de 3,5 vezes nas chances de desenvolvimento de medo moderado do COVID-19 (p<0,001). A presença de um medo intenso do COVID-19 aumentou em 17,15 vezes as chances de desenvolvimento de sintomas de ansiedade (p<0,001), enquanto a presença de um medo moderado aumentou essas chances em 3,12 vezes (p<0,001). Ademais, a presença de medos intensos (p=0,01) ou moderados (p=0,018) do COVID-19 aumentou 2,47 e 1,84 vezes, respectivamente, as chances de desenvolvimento de sintomatologias dolorosas relacionadas à DTM nessa população. CONCLUSÃO: A presença dos sintomas dolorosos da DTM foi possivelmente influenciada pelo medo do COVID-19. Isso, por sua vez, esteve relacionado à presença de sintomas de ansiedade e de depressão, reportados pela população-alvo deste estudo.

Early life adversity across different cell- types in the brain.

Early life adversity (ELA)- which includes physical, psychological, emotional, and sexual abuse is one of the most common predictors to diverse psychopathologies later in adulthood. As ELA has a lasting impact on the brain at a developmental stage, recent findings from the field highlighted the specific contributions of different cell types to ELA and their association with long lasting consequences. In this review we will gather recent findings describing morphological, transcriptional and epigenetic alterations within neurons, glia and perineuronal nets and their associated cellular subpopulation. The findings reviewed and summarized here highlight important mechanisms underlying ELA and point to therapeutic approaches for ELA and related psychopathologies later in life.

Endoscopic lumbar sympathectomy as a treatment option for primary erythromelalgia - case report and review.

Erythromelalgia is a rare disease, involving pain, edema, redness, and hyperthermia in the limbs. It is extremely refractory to drugs, has no defined treatment, and causes psychological comorbidities in the patient. We describe a case of erythromelalgia involving a 17-year-old boy who had been suffering from the disease for almost 4 years prior to finding an effective treatment. A bilateral endoscopic lumbar sympathectomy was performed, limited to L2 and L3 resections. Four weeks after the procedure, the patient's symptoms were significantly mitigated and at 8 months follow-up he remained almost asymptomatic. Endoscopic lumbar sympathectomy was an effective treatment for primary erythromelalgia in this teenager, with exceptional reduction of his symptoms.

Eritromelalgia é uma doença rara caracterizada por dor, edema, eritema e hipertermia nos membros. É extremamente refratária a medicamentos e não tem um tratamento definido, causando comorbidades psicológicas para o paciente. Descrevemos o caso de um menino de 17 anos que possuía eritromelalgia há quase 4 anos antes de ser submetido a um tratamento efetivo. Foi realizada simpatectomia lombar endoscópica bilateral limitada à ressecção dos gânglios L2 e L3. Após 4 semanas do procedimento, o paciente teve diminuição significativa dos seus sintomas e, com 8 meses de seguimento, permanece praticamente assintomático. A simpatectomia lombar endoscópica foi um tratamento eficaz para eritromelalgia primária em um adolescente, com redução excepcional dos seus sintomas.

In vivo osseointegration evaluation of implants coated with nanostructured hydroxyapatite in low density bone.

OBJECTIVE: This in vivo study, aimed to biomechanically, histomorphometrically and histologically evaluate an implant surface coated with nanostructured hydroxyapatite using the wet chemical process (biomimetic deposition of calcium phosphate coating) when compared to a dual acid-etching surface. MATERIAL AND METHODS: Ten sheep (2-4 years old) received 20 implants, 10 with nanostructured hydroxyapatite coating (HAnano), and 10 with dual acid-etching surface (DAA). The surfaces were characterized with scanning electron microscopy and energy dispersive spectroscopy; insertion torque values and resonance frequency analysis were measured to evaluate the primary stability of the implants. Bone-implant contact (BIC) and bone area fraction occupancy (BAFo) were evaluated 14 and 28 days after implant installation. RESULTS: The HAnano and DAA groups showed no significant difference in insertion torque and resonance frequency analysis. The BIC and BAFo values increased significantly (p<0.05) over the experimental periods in both groups. This event was also observed in BIC value of HAnano group. The HAnano surface showed superior results compared to DAA after 28 days (BAFo, p = 0.007; BIC, p = 0.01). CONCLUSION: The results suggest that the HAnano surface favors bone formation when compared to the DAA surface after 28 days in low-density bone in sheep.

Religiosity and religious and spiritual struggle and their association to depression and anxiety among adolescents admitted to inpatient psychiatric units.

This study examines the relationship between religious and spiritual (R/S) struggle and religiosity with depression and anxiety in adolescents admitted to inpatient psychiatric units of a pediatric hospital in the Midwest of the United States. We administered four self-reported scales to 71 adolescents (ages 13-17) to assess religiosity, R/S struggle, depression, and anxiety. The prevalence of R/S struggle among this population was high (88.73%). Significant associations were found between R/S struggle and depression and anxiety, linking greater R/S struggles with more severe depression or anxiety. However, no significant associations between religiosity and depression and anxiety were noted. By examining the prevalence of R/S struggle among this population and its relationship to depression and anxiety, this study contributes to the expanding research on the impact of religion and spirituality on the psychological well-being of adolescents.

"Non-metastatic, Castration-resistant Prostate Cancer: Diagnostic and Treatment Recommendations by an Expert Panel from Brazil".

INTRODUCTION: Non-metastatic, castration-resistant prostate cancer (nmCRPC) is an important clinical stage of prostate cancer, prior to morbidity and mortality from clinical metastases. In particular, the introduction of novel androgen-receptor signaling inhibitors (ARSi) has changed the therapeutic landscape in nmCRPC. Given recent developments in this field, we update our recommendations for the management of nmCRPC. METHODS: A panel of 51 invited medical oncologists and urologists convened in May of 2021 with the aim of discussing and providing recommendations regarding the most relevant issues concerning staging methods, antineoplastic therapy, osteoclast-targeted therapy, and patient follow-up in nmCRPC. Panel members considered the available evidence and their practical experience to address the 73 multiple-choice questions presented. RESULTS: Key recommendations and findings include the reliance on prostate-specific antigen doubling time for treatment decisions, the absence of a clear preference between conventional and novel (i.e., positron-emission tomography-based) imaging techniques, the increasing role of ARSis in various settings, the general view that ARSis have similar efficacy. Panelists highlighted the slight preference for darolutamide, when safety is of greater concern, and a continued need to develop high-level evidence to guide the intensity of follow-up in this subset of prostate cancer. DISCUSSION: Despite the limitations associated with a consensus panel, the topics addressed are relevant in current practice, and the recommendations can help practicing clinicians to provide state-of-the-art treatment to patients with nmCRPC in Brazil and other countries with similar healthcare settings.

Survival and complications of zygomatic implants compared to conventional implants reported in longitudinal studies with a follow-up period of at least 5 years: A systematic review and meta-analysis.

BACKGROUND: Zygomatic implants (ZI) have been frequently indicated to rehabilitate patients with extensive atrophies in alternatives to major bone reconstructions. It can be installed inside the maxillary sinus, called instrasinus zygomatic implant (IZI) or outside the maxillary sinus (EZI), depending on the surgery technique. OBJECTIVE: To evaluate the survival and complication rates of ZI in longitudinal studies when compared with conventional implants (CI). METHODS: An electronic search was performed in five databases and in Gray literature for articles published until April, 2022. The eligibility criteria comprised observational cohort studies (prospective or retrospective) and randomized clinical trials (RCTs) with at least 5 years of follow-up, reporting survival rate of ZI versus CI. A meta-analysis was conduct with 18 studies. RESULTS: A total of 5434 implants (2972 ZI and 2462 CI) were analyzed in 1709 patients. The mean survival rate was 96.5% ± 5.02 and 95.8% ± 6.36 for ZI and CI, respectively (mean follow-up time of 78 months). There were observed no statistically significant between ZI and CI in prospective studies (risk ratio [RR] of 1.21; 95% confidence intervals [CIs]: 0.28 to 5.28; chi-squared [Chi2 ] = 11.37; I2  = 56%; degrees of freedom [df] = 5; z-score = 0.25; P = 0.80), retrospective studies IZI (RR of 1.29; 95% CIs: 0.52 to 3.23; Chi2  = 4.07; I2  = 2%; df = 4; z-score = 0.55; P = 0.58) and retrospective studies EZI (RR of 0.72; 95% CIs: 0.31 to 1.66; Chi2  = 1.99; I2  = 0%; df = 3; z-score = 0.78; P = 0.44). The biological complications most related to ZI was sinusitis, followed by infection and oroantral communication. CONCLUSION: ZI have a high long-term survival rate (96.5% with a mean of 91.5 months of follow-up), showing no significant difference when compared with CI. The most prevalent biological complication is sinusitis, being most commonly to the IZI technique. This systematic review (SR) was registered in INPLASY under number INPLASY202280025.

Endoscopic lumbar sympathectomy as a treatment option for primary erythromelalgia - case report and review / Simpatectomia lombar endoscópica como escolha de tratamento para eritromelalgia primária - relato de caso e revisão

Abstract Erythromelalgia is a rare disease, involving pain, edema, redness, and hyperthermia in the limbs. It is extremely refractory to drugs, has no defined treatment, and causes psychological comorbidities in the patient. We describe a case of erythromelalgia involving a 17-year-old boy who had been suffering from the disease for almost 4 years prior to finding an effective treatment. A bilateral endoscopic lumbar sympathectomy was performed, limited to L2 and L3 resections. Four weeks after the procedure, the patient's symptoms were significantly mitigated and at 8 months follow-up he remained almost asymptomatic. Endoscopic lumbar sympathectomy was an effective treatment for primary erythromelalgia in this teenager, with exceptional reduction of his symptoms.

Resumo Eritromelalgia é uma doença rara caracterizada por dor, edema, eritema e hipertermia nos membros. É extremamente refratária a medicamentos e não tem um tratamento definido, causando comorbidades psicológicas para o paciente. Descrevemos o caso de um menino de 17 anos que possuía eritromelalgia há quase 4 anos antes de ser submetido a um tratamento efetivo. Foi realizada simpatectomia lombar endoscópica bilateral limitada à ressecção dos gânglios L2 e L3. Após 4 semanas do procedimento, o paciente teve diminuição significativa dos seus sintomas e, com 8 meses de seguimento, permanece praticamente assintomático. A simpatectomia lombar endoscópica foi um tratamento eficaz para eritromelalgia primária em um adolescente, com redução excepcional dos seus sintomas.

Low-Level Light Therapy in Association with Intense Pulsed Light for Meibomian Gland Dysfunction.

Purpose: To study the clinical benefit of low-level light therapy when associated with intense pulsed light for the treatment of meibomian gland dysfunction. Methods: An observational study. Two groups of patients that were treated with IPL were considered: group 1 (31 subjects, 62 eyes), intense pulsed light followed by low-level light therapy and group 2 (31 subjects, 62 eyes) intense pulsed light alone. In both groups, treatments were performed in 3 sessions and subjects were evaluated at baseline and 3 weeks after the last treatment session. Values are shown as mean difference ± standard deviation. Results: We observed a significant improvement in OSDI-12 score and lipid layer thickness, in both groups (-22.7±17.5, p<0.001 in group 1 and -23.6±23.8, p<0.001 in group 2 for OSDI and +18.6 ± 37.0, p<0.001 in group 1 and +19.9 ± 26.4, p<0.001 in group 2 for lipid layer thickness). Despite no differences between groups at baseline (p=0.469), only group 1 had a significant improvement in Schirmer test (+1.6±4.8, p=0.009 in group 1 and +1.7±6.9, p=0.057 in group 2). No significant side effects were noted. No patient in any group felt subjectively "worse" after the treatment. Conclusion: Intense pulsed light seems effective and safe for the treatment of meibomian gland dysfunction, improving symptoms and the tear film lipid layer. This study shows no strong evidence of the benefit of low-level light therapy, but it shows weak evidence that it may further improve aqueous tear production.

Targeted Therapy for Locally Advanced or Metastatic Urothelial Cancer (mUC): Therapeutic Potential of Sacituzumab Govitecan.

Urothelial carcinoma is the second most frequent genitourinary malignancy. Despite the poor prognosis, new treatment options have emerged and have expanded the therapeutic landscape for the disease. Although major improvements have been achieved, many patients experience rapid disease progression and low responses in subsequent lines of therapy. Sacituzumab govitecan is an ADC that targets Trop-2, which is highly expressed in urothelial cancers. Promising results in early clinical trials have led to further drug development which confirmed encouraging efficacy. Sacituzumab govitecan has been given accelerated approval in 2021 for patients with locally advanced and metastatic urothelial cancer who previously received a platinum containing chemotherapy and either a programmed death receptor-1 or programmed death ligand inhibitor. The results are promising, with encouraging efficacy and safety, however responses are not universal. There is a growing comprehension of mechanisms of resistance and predictive biomarkers that are crucial to improving outcomes. In this review, we summarize the current knowledge on antibody-drug conjugates and the clinical findings that led to the approval of Sacituzumab govitecan and discuss the therapeutic potential of new combinations, mechanisms of resistance and predictive biomarkers.

Impact of COVID-19 pandemic on the ocular surface.

BACKGROUND: There have been increased reports of dry eyes in the coronavirus disease 2019 (COVID-19) pandemic era. AIM: To analyze the differences in tear film properties from pre- and post-pandemic of the COVID-19 era. METHODS: It was a retrospective comparative study. Patients were divided into three groups according to the data of multimodal ocular surface evaluation: (1) Group 1 if it was before Portugal lockdown decision (from August 2019 to March 2020); (2) Group 2 if it was after Portugal lockdown decision but without mask mandate (from April 2020 to October 2020); and (3) Group 3 if it was after Portugal lockdown but with mask mandate in health public highway (from November 2020 to April 2021). The following variables were analyzed: Lipid layer thickness, blink rate, Schirmer test, tear meniscus height, tear osmolarity, non-invasive break-up time, and loss area of the meibomian glands. RESULTS: The study included 548 eyes of 274 patients, aged 18 years to 89 years, with a mean age of 66.15 ± 13.40 years at the time of multimodal ocular surface evaluation. Compared to group 1: (1) Mean lipid layer thickness was better in group 2 (P = 0.001) and group 3 (P < 0.001); (2) Schirmer test was similar in group 2 (P = 0.576) and better in group 3 (P = 0.002); (3) Tear osmolarity and loss area of the meibomian glands were worse in group 2 (P = 0.031 and P < 0.001, respectively) and in group 3 (both with P < 0.001); (4) Blink rate and tear meniscus height were similar in group 2 (P = 0.821 and P = 0.370, respectively) and worse in group 3 (P < 0.001 and P = 0.038, respectively); and (5) Non-invasive break-up time was worse in group 2 (P = 0.030) and similar in group 3 (P = 0.263). CONCLUSION: Our study demonstrated that differences existed in tear film properties comparing data from the pre- and post-pandemic of the COVID-19 era.

Profiling cell-type specific gene expression in post-mortem human brain samples through laser capture microdissection.

The transcriptome of a cell constitutes an essential piece of cellular identity and contributes to the multifaceted complexity and heterogeneity of cell-types within the mammalian brain. Thus, while a wealth of studies have investigated transcriptomic alterations underlying the pathophysiology of diseases of the brain, their use of bulk-tissue homogenates makes it difficult to tease apart whether observed differences are explained by disease state or cellular composition. Cell-type-specific enrichment strategies are, therefore, crucial in the context of gene expression profiling. Laser capture microdissection (LCM) is one such strategy that allows for the capture of specific cell-types, or regions of interest, under microscopic visualization. In this review, we focus on using LCM for cell-type specific gene expression profiling in post-mortem human brain samples. We begin with a discussion of various LCM systems, followed by a walk-through of each step in the LCM to gene expression profiling workflow and a description of some of the limitations associated with LCM. Throughout the review, we highlight important considerations when using LCM with post-mortem human brain samples. Whenever applicable, commercially available kits that have proven successful in the context of LCM with post-mortem human brain samples are described.