Fruquintinib-Induced Cerebellar Hemorrhage in Left-Sided Descending Metastatic Colorectal Adenocarcinoma: A Case Report and Risk Assessment.

Colorectal adenocarcinoma is the most prevalent form of colorectal cancer, representing the majority of cases in the United States. The disease is driven by a series of genetic mutations, including alterations in the adenomatous polyposis coli (APC), Kirsten rat sarcoma viral oncogene homolog G12D (KRAS), human epidermal growth factor receptor 2 immunohistochemistry 3+ (HER-2 IHC3+), checkpoint kinase 2 (CHEK-2) and tumor protein P53 (TP53) genes, which lead to malignant transformation. While the standard treatment for metastatic colorectal cancer (mCRC) typically involves chemotherapy and targeted therapies, many patients experience disease progression, necessitating the exploration of novel treatments. Fruquintinib, a highly selective vascular endothelial growth factor (VEGFR) inhibitor, has emerged as a promising option for mCRC patients who have exhausted conventional therapies. However, its use is associated with significant bleeding risks, including rare but severe complications such as cerebellar hemorrhage. This case report presents a patient with mCRC who developed a cerebellar hemorrhage shortly after initiating fruquintinib therapy, highlighting the need for careful patient monitoring and individualized risk assessment to mitigate such serious adverse events.

Clozapine may consistently protect from suicidal behaviors while other antipsychotics may lack a specific protective effect: a comprehensive VigiBase study interpreted in the context of the prior literature.

BACKGROUND: In the United States clozapine was first approved for treatment-resistant schizophrenia and then for suicidality in schizophrenia psychoses. Systematic reviews support clozapine's anti-suicidal effect, but the forensic literature stresses its lethality during overdoses. RESEARCH DESIGN AND METHODS: Clozapine reports to the international pharmacovigilance database (VigiBase) were analyzed for suicidal ideation, suicide attempts, intentional overdose, and completed suicides from introduction to 1 January 2024. VigiBase uses the information component (IC) as a disproportionality analysis. RESULTS: The clozapine ICs (range: other antipsychotics) were: 1) suicidal ideation IC = 0.570 with IC025 = 0.454 to IC975 = 0.680 (IC = 3.568 for aripiprazole and 1.729 for risperidone), 2) suicide attempt IC = 1.428 with IC025 = 1.323 to IC975 = 1.529 (IC = 4.150 for quetiapine and 2.968 for risperidone), 3) intentional overdose: IC = 0.995 with IC025 = 0.864 to IC975 = 1.120 (IC = 4.080 for quetiapine and 1.957 for aripiprazole), and 4) completed suicide IC = 1.133 with IC025 = 1.026 to IC975 = 1.235 (IC = 4.648 for quetiapine and 2.160 for risperidone). In summary, all clozapine ICs were significantly lower. We found 2391 clozapine-treated patients on the suicidality spectrum (627 cases with suicidal ideation, 752 with suicide attempt, 488 with intentional overdose and 731 with completed suicide) but many were taking other antipsychotics. The most frequent reporting countries were the United States, the United Kingdom, and Croatia. CONCLUSION: This pharmacovigilance study, with all its inherent limitations, provides independent proof, not overlapping with prior literature, that clozapine may have specific strong anti-suicidal effects that do not appear to be present in other antipsychotics. Further VigiBase studies are needed to compare the lethality of an intentional overdose of clozapine (14.3%) with other antipsychotics.

Noninvasive Therapies: A Forthcoming Approach to Parkinson's Treatment.

In this review, we have discussed the invasive and non-invasive treatment options for Parkinson's Disease (PD) following their safety, specificity, and reliability. Initially, this study has highlighted the invasive treatment options and the side effects they possess. A deep understanding of L-Dopa treatment, as oral or infusion, and the use of dopamine agonists has indicated that there is a need to acquire an alternative treatment for PD. The combined therapy with L-Dopa has been proven to affect PD, but with some limitations, such as mild to chronic side effects, with particular requirements of age and health of the patient and a large amount of expenditure. In the discussion of noninvasive methods to treat PD, we have found that this approach is comparatively slow and requires repetitive sessions, but is safe, effective, and reliable at any stage of PD. Electroconvulsive therapy has revealed its effectiveness in various neurological diseases, including PD. Transcranial current stimulation (direct or alternative) has already been shown to have an alleviative response to PD symptoms. Transcranial magnetic stimulations and other strategies of using the magnetic field for potential treatment options for PD need to be explored further imminently.

Vitamin B12 Deficiency in Patients Taking Metformin: Pathogenesis and Recommendations.

Metformin is a cornerstone therapy for type 2 diabetes mellitus due to its glucose-lowering efficacy and additional benefits such as reducing cardiovascular mortality. However, accumulating evidence suggests an association between long-term metformin use and vitamin B12 deficiency, which can lead to serious clinical consequences. This review aims to synthesize current knowledge on the pathogenesis, prevalence, clinical implications, and management of metformin-induced vitamin B12 deficiency. Given the significant clinical implications, it is crucial to monitor and manage vitamin B12 levels in patients using metformin. This review emphasizes the importance of early detection and supplementation to prevent adverse outcomes. By analyzing the current evidence, the review aims to inform healthcare professionals about best practices for managing vitamin B12 deficiency in patients on metformin, offering insights to guide future clinical practices and research directions.

Appetite hormones, neuropsychological function and methylphenidate use in children with attention-deficit/hyperactivity disorder.

Appetite hormones may play a significant role in neuronal excitability and synaptic plasticity and may also affect brain function development. This study aimed to explore the role of appetite hormones in attention deficit/hyperactivity disorder (ADHD), including aspects of pathophysiology, pharmacotherapy, and side effects. We recruited 119 patients with ADHD who were undergoing methylphenidate treatment (ADHD+MPH), 77 unmedicated ADHD patients (ADHD-MPH), and 87 healthy controls. Blood samples were collected from all participants to examine serum levels of orexin A, ghrelin, leptin, and adiponectin. Behavioral symptoms were assessed using the Swanson, Nolan, and Pelham Rating Scale, and visual and auditory attention were evaluated using computerized neuropsychological tests. The side effects of methylphenidate treatment were measured using Barkley's Side Effects Rating Scale. Orexin levels in the control group were significantly higher than in the ADHD-MPH (p=0.037) and ADHD+MPH (p<0.001) groups; additionally, orexin levels in the ADHD-MPH group were significantly higher than in the ADHD+MPH group (p=0.032). Leptin levels in both the ADHD+MPH (p=0.011) and ADHD-MPH (p=0.011) groups were significantly lower than in the control group. Ghrelin levels were positively associated with auditory attention across all ADHD groups (p=0.015). Furthermore, ghrelin levels were positively correlated with methylphenidate dosage (p=0.024), and negatively correlated with methylphenidate side effects (p=0.044) in the ADHD+MPH group. These findings provide further insight into the relationships between appetite hormones, pharmacotherapy, and ADHD. Orexin A and leptin are associated with the etiology of ADHD, while orexin A and ghrelin play important roles in attention deficits and methylphenidate usage in ADHD.

Reimagining the ADR Alert Card: a novel approach to recurrence prevention in low-cost settings for adverse drug reactions.

OBJECTIVES: Adverse drug reactions (ADRs) are among the leading standalone causes of morbidity and hospitalisation and contribute substantially to an increase in healthcare expenditure. Repeat ADR events, although difficult to quantify, are a recognised problem that lead to preventable suffering for the patient. The current approaches for the prevention of ADR recurrence in low/middle-income countries range from inefficient to non-existent. There is very little literature that focuses on the preventability of ADRs in such settings. This study aimed to develop the ADR Alert Card, an economical innovation designed as a stop gap in preventing ADR recurrence, and to evaluate its utility by validating the system through input from medical professionals. METHODS: The ADR Alert Card was validated and registered with the Copyrights Office of the Government of India. To obtain the opinion of healthcare professionals and gauge the status quo in prevention of ADR recurrence, we conducted an online descriptive cross-sectional study over a period of 6 months. RESULTS: The survey received 218 responses. Demographics varied, ranging across different healthcare specialties and years of experience. Our study found that existing practice in ADR recurrence prevention was inadequate, and most healthcare workers were unaware of an alternative approach. Unique solutions were provided by the respondents, with the majority favouring a card format for preventing recurrence. CONCLUSIONS: After being introduced to the ADR Alert Card, there was an overwhelming consensus on the utility and practicality of this card in preventing ADR recurrence.

Safety assessment of asenapine in the FAERS database: real adverse event analysis and discussion on neurological and psychiatric side effects.

PURPOSE: This study aims to comprehensively assess the safety of Asenapine by conducting an comprehensive statistical analysis of adverse event reports in the FAERS database, with a particular focus on potential adverse reactions related to its use in the treatment of psychiatric disorders. METHODS: Event reports from the first quarter of 2009 to the third quarter of 2023 were collected and analyzed. Detailed examinations of gender, age, reporter identity, and other aspects were conducted to reveal the fundamental characteristics of Asenapine-related adverse events. Signal mining techniques were employed to systematically evaluate various adverse reactions associated with Asenapine. RESULTS: The study found that adverse event reports involving Asenapine were more common among female patients, with the age group mainly distributed between 18 and 45 years. Physicians were the primary reporters of adverse events, and psychiatric disorders, neurological disorders, and gastrointestinal disorders were the most common areas affected by adverse reactions. In addition to known adverse reactions, potential risks not mentioned in the drug label were identified, such as anosognosia, attentional drift, and psychogenic compensation disorder. CONCLUSION: Asenapine carries the risk of various adverse reactions alongside its therapeutic effects. In clinical practice, physicians should closely monitor the occurrence of neurological disorders, psychiatric disorders, and gastrointestinal system disorders.

The risk of psychiatric disorders in finasteride users with benign prostatic hyperplasia and androgenetic alopecia: A population-based case-control study.

BACKGROUND: There is a long-standing debate if finasteride, a medication used to treat benign prostatic hyperplasia (BPH) and androgenetic alopecia (AGA), can cause psychiatric side effects. OBJECTIVE: The goal of this large-scale population-based study was to determine whether finasteride therapy for BPH and AGA is associated with the emergence of mental health conditions. METHODS: This observational case-control study compared the data from patients with BPH who received finasteride 5 mg daily and patients with AGA who received finasteride 1 mg daily with age- and gender-matched controls. The incidence of psychological health outcomes such as depression, anxiety, neuroses, bipolar disorder, schizophrenia, psychoses and alcohol abuse within 2 years of the initiation of finasteride therapy has been evaluated and compared between the finasteride groups and controls. RESULTS: The BPH group included 307 men with a mean age of 61.5 (±17.4) years and 1218 controls. Mental health outcomes recorded in 2.3% of the patients, with no significant increase in rate when compared to controls. The AGA group consisted of 23,227 men with a mean age of 31.4 (±10.3) years and 39,444 controls. Only One percent of AGA patients developed psychiatric disorders. In comparison to controls, patients with AGA had higher rates of anxiety and depression (0.6% vs. 0.4%, p = 0.04, and 0.5% vs. 0.4%, p = 0.007, respectively). In multivariate regression models, finasteride was found as one of the risk factors for anxiety (OR 1.449, p = 0.002) and depression (OR 1.439, p = 0.003) when stratified to age, sector, socioeconomic status and comorbidities. CONCLUSIONS: According to our research, finasteride users had a very low rate of adverse mental health effects, with no increase in psychological sequelae in BPH patients and a slight increase in anxiety and depression in AGA patients.

Adverse Events in Anti-PD-1-Treated Adjuvant and First-Line Advanced Melanoma Patients.

Introduction: The difference in incidence and severity of anti-PD-1 therapy-related adverse events (irAEs) between adjuvant and advanced treated melanoma patients remains unclear, as no head-to-head studies have compared these groups. Methods: This multi-center cohort study analyzed melanoma patients treated with anti-PD-1 in adjuvant or advanced settings between 2015 and 2021. Comorbidities and ECOG performance status were assessed before treatment, and grade III-IV irAEs were monitored during treatment. Univariate and multivariate regression analyses were conducted to identify factors associated with irAE development. Results: A total of 1465 advanced melanoma patients and 908 resected melanoma patients received anti-PD-1 therapy. Adjuvant-treated patients were younger, with a median age of 63 years compared to 69 years in the advanced group (p < 0.01), and had a better ECOG performance status (p < 0.01). Comorbidities were seen more frequently in advanced melanoma patients than in those receiving adjuvant treatment, 76% versus 68% (p < 0.01). Grade III-IV irAEs occurred in 214 (15%) advanced treated patients and in 119 (13%) adjuvant-treated patients. Multivariate analysis showed an increased risk of severe irAE development with the presence of any comorbidity (adjusted OR 1.22, 95% CI 1.02-1.44) and ECOG status greater than 1 (adjusted OR 2.00, 95% CI 1.20-3.32). Adjuvant therapy was not associated with an increased risk of irAE development compared to advanced treatment (adjusted OR 0.95, 95% CI 0.74-1.21) after correcting for comorbidities and ECOG performance score. Anti-PD-1 therapy was halted due to toxicity (any grade irAE) more often in the adjuvant setting than in the advanced setting, 20% versus 15% (p < 0.01). Conclusions: Higher ECOG performance status and presence of any comorbidity were independently associated with an increased risk of Grade III-IV irAE in adjuvant and advanced treated melanoma patients. Patients treated in the adjuvant setting did not have an increased risk of developing severe irAEs compared to advanced melanoma patients. These findings are of clinical significance in consulting patients for adjuvant anti-PD-1 treatment.

[Physical medicine for coincidence of cancer and inflammatory rheumatic disease : What speaks in favour and what to consider?] / Physikalische Medizin bei Koinzidenz einer Krebserkrankung und entzündlich-rheumatischen Erkrankung : Was spricht dafür und worauf ist zu achten?

The coincidence of an inflammatory rheumatic and a malignant disease causes a physical, cognitive and psychological reduction in performance. The prescription of physical therapy is therefore essential to address safety issues associated with both diseases, as well as side effects associated with antirheumatic and antineoplastic therapy that can impact the treatment. It is important to perform a risk assessment prior to physical therapy to identify potential safety issues and to determine baseline physical and functional status. In this review article descriptive information and the current literature on the safety of physical therapy interventions for people with rheumatic and malignant disease are highlighted, taking the disease process, treatment side effects and associated precautions and contraindications into account.

[Gender medicine in peritoneal diseases]. / Gendermedizin bei peritonealen Erkrankungen.

Diseases of the peritoneum are divided into benign and malignant, whereby malignant diseases are more frequent. The incidence of peritoneal metastases is difficult to determine as they are frequently not listed separately in cancer databases and registries. Peritoneal metastases can be caused by many primary tumors but are particularly frequent in gastric, ovarian and colorectal carcinomas. Systemic chemotherapy shows gender-specific differences in the tolerability, especially gastrointestinal side effects and hematological toxicity occur more often in women. Surgical treatment options in selected patients include cytoreductive surgery with or without hyperthermic intraperitoneal chemoperfusion (HIPEC). The treatment recommendations depend on the primary tumor entity and the stage of the disease. Hysterectomy and/or salpingo-oophorectomy is often necessary during cytoreductive surgery. As the incidence of cancerous diseases is increasing in younger patients, the aspect of fertility is becoming increasingly more important. The iatrogenically induced menopause is another aspect that needs to be addressed after these types of procedures. Women with gastric and colorectal cancer tend to have a slightly better survival rate, especially in localized tumors; however, in advanced tumor stages the survival rates are comparable. Even if gender-specific differences in incidence, treatment response and adverse events are conspicuous, there is so far no exact explanation for these differences. More studies are needed in order to treat both genders as adequately as possible, with low adverse events and to achieve the best possible outcome.

S2k-Guideline Non-hormonal Contraception, Part 1: Natural Family Planning, Lactational Amenorrhea, Barrier Methods, Coitus Interruptus: Guideline of the DGGG, OEGGG and SGGG (S2k-Level, AWMF Registry No. 015 - 095, January 2024).

Aim This official guideline was published and coordinated by the DGGG, OEGGG and SGGG with the involvement of other medical societies. The aim was to provide a consensus-based overview of non-hormonal forms of contraception based on an evaluation of the relevant literature. The first part of these summarized statements and recommendations presents natural family planning methods such as lactational amenorrhea, barrier methods and coitus interruptus. The second part will focus on intrauterine devices and sterilization methods. Methods This S2k-guideline was developed by representative members from different medical professions on behalf of the guidelines commission of the DGGG, OEGGG and SGGG using a structured consensus process. Recommendations The guideline provides recommendations on the indications for, safety of use, benefits, and limitations of the different methods as well as recommendations on providing advice and other aspects of non-hormonal contraception. Natural family planning methods, lactational amenorrhea, barrier methods and coitus interruptus are discussed.

S2k-Guideline Non-hormonal Contraception, Part 2: Intrauterine Devices and Sterilization: Guideline of the DGGG, OEGGG and SGGG (S2k-Level, AWMF Registry No. 015 - 095, January 2024).

Aim This official guideline was published and coordinated by the DGGG, OEGGG and SGGG with the involvement of other medical societies. The aim was to provide a consensus-based overview of non-hormonal forms of contraception based on an evaluation of the relevant literature. The first part of these summarized statements and recommendations presents natural family planning methods such as lactational amenorrhea, barrier methods and coitus interruptus. The second part focuses on intrauterine devices and sterilization. Methods This S2k-guideline was developed by representative members from different medical professions on behalf of the guidelines commission of the DGGG, OEGGG and SGGG using a structured consensus process. Recommendations The guideline provides recommendations on the indications for, safety of use, benefits, and limitations of the different methods as well as recommendations on providing advice and other aspects of non-hormonal contraception. This summary presents recommendations and statements about intrauterine devices and female and male sterilization.

Treatment-emergent sexual dysfunctions due to antidepressants: A primer on assessment and management strategies.

Antidepressants (ADs) are among the most commonly prescribed drugs worldwide. Persons with mental illness taking ADs commonly report sexual dysfunction (SD) related to treatment. A brief discussion on the neurobiology of sexual functioning and mechanism of treatment-emergent SD (TESD) was performed. The incidence of prevalence of TESD in various studies has been reviewed. TESD impacts patients as it frequently leads to nonadherence, while psychiatrists have challenges in proceeding forward with treatment in such patients. Assessment of patients with suspected TESD is described with a focus on practical tips for clinicians. Five strategies (watchful waiting, drug holiday, downward titration, switching, and add-on therapy) to manage TESD have been extensively discussed with evidence in the literature. Each strategy comes with its own bag of advantages and drawbacks, which have been pointed out for simplicity. A detailed discussion on individual pharmacological strategies is given, and options for non-pharmacological management that can be tried are enlisted. Common clinical case scenarios have been discussed to incorporate the implementation of this literature.

Myxedema Coma: Recognition of a Rare Endocrine Emergency.

An 82-year-old patient with multiple comorbidities presented to the emergency department with progressive dyspnea, orthopnea, and anorexia. Despite initial treatment for community-acquired pneumonia and decompensated heart failure, her condition deteriorated, manifesting as severe hypotension, bradycardia, and refractory hypothermia. A detailed medical history and extensive systematic investigation led to the documentation of hypothyroidism complicated by myxedema coma, in the context of chronic amiodarone use and precipitated by sepsis. Treatment with intravenous levothyroxine and glucocorticoids resulted in significant clinical improvement, leading to eventual hospital discharge. This case highlights the complexity and diagnostic challenges of myxedema coma, emphasizing the importance of early recognition, appropriate application of diagnostic scoring systems, and describing key aspects of the proper management of this rare endocrine emergency, whose symptoms and clinical signs are nonspecific.

Type 1 diabetes mellitus following COVID-19 vaccination: a report of two cases and review of literature.

Severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) infection, which led to the coronavirus 2019 (COVID-19) pandemic, has promoted the development of novel therapeutic agents and vaccines to combat the global spread of the virus. While the COVID-19 vaccines approved thus far have proven to be effective in clinical settings, there have been reports of autoimmune diseases occurring following vaccination, including autoimmune/inflammatory syndrome induced by adjuvant syndrome. We herein report two cases of type 1 diabetes mellitus that occurred following COVID-19 vaccination and provide a literature review. Both cases received multiple vaccinations as recommended to ensure optimal antibody titers. Moreover, the HLA associated with susceptibility to type 1 diabetes was prototypic in both cases. This indirect evidence suggests that the COVID-19 vaccines may be implicated in the pathogenesis of type 1 diabetes. Further case reports to establish a clearer understanding of a potential association are warranted. Supplementary Information: The online version contains supplementary material available at 10.1007/s13340-024-00695-9.