Bilateral acute depigmentation of the iris (BADI) and bilateral acute iris transillumination (BAIT): A case series from a center in Brazil

ABSTRACT Bilateral acute depigmentation of the iris and bilateral acute iris transillumination (BAIT) are similar clinical entities. The former causes acute-onset depigmentation of the iris stroma without transillumination, whereas the latter causes depigmentation of the iris pigment epithelium with transillumination. The etiopathogenesis of these conditions is not yet fully understood, but the proposed causes include the use of systemic antibiotics (especially moxifloxacin) and viral triggers. We present a case series of five female patients with a mean age of 41 (32-45) years, all of whom suffered acute onset of bilateral pain and redness of the eyes after moxifloxacin use (oral or topical). It is important for ophthalmologists to be aware of the two forms of iris depigmentation since this case series suggests that SARS-CoV-2 or its empirical treatment with moxifloxacin may trigger iris depigmentation. If this is the case, clinicians will likely see increased incidences of bilateral acute depigmentation of the iris and bilateral acute iris transillumination during and after the COVID-19 pandemic.

Eosinophil-related diseases during treatment with glucagon-like peptide one receptor (GLP-1 RA): a case report and review of the literature.

Glucagon-like peptide one-receptor agonists (GLP-1 RA) are drugs that differ in their pharmacological composition and homology to human GLP-1 and are used most frequently for the treatment of type 2 diabetes and weight loss. There are isolated reports of eosinophilic adverse reactions associated with GLP-1 RA. We present the case of a 42-year-old female patient who, after starting weekly subcutaneous semaglutide, developed eosinophilic fasciitis with favorable clinical evolution after the discontinuation of semaglutide and the initiation of immunosuppression. A review of the eosinophilic adverse events that have been previously reported with GLP-1 RA is provided.

Case report of possible iatrogenic Cushing's disease with low-dose prednisone to treat dermal filler hypersensitivity.

OBJECTIVES: The aim of this article is to report a case of iatrogenic Cushing's disease associated with a delayed inflammatory response due to a facial dermal filler procedure. METHODS: A case report according to CARE guidelines was performed. A delayed inflammatory reaction due to dermal filler injection resulted in iatrogenic Cushing's disease in a patient with no comorbidities or allergies. RESULTS: Prolonged use of glucocorticoids can cause adverse effects, such as iatrogenic Cushing's disease. Dermal fillers have a very low incidence of complications, but these need to be discussed with patients. Drugs used to treat delayed inflammatory reaction include antibiotics, antihistamines, steroids, and intralesional hyaluronidase. Reversal of dermal fillers should be explained to the patient and included in the written consent. CONCLUSIONS: Due to patient non-compliance and possible adverse effects of steroid medications, physicians should consider limiting their prescriptions of steroid medications to no more than 2 weeks and require frequent follow-up to discuss hyaluronidase if the condition returns off of steroid medication. In addition, it may be advisable to only treat with one filler brand, especially in the same session as this may be a risk factor.

Successful Pre-Clinical Management of Irinotecan-Debilitated Animals: A Protein- Based Accessory Phytomedicine.

BACKGROUND: Calotropis procera is a laticiferous plant (Apocynaceae) found in tropical regions all over the world. The ultrastructural characteristics of laticifers, their restricted distribution among different taxonomic groups, and in some species in each clade, as peptidases from latex, make them very attractive for biological analysis. OBJECTIVE: The study aims to investigate the effects of LP-PII-IAA (laticifer protein (LP) sub-fraction II (PII) of C. procera presenting an iodoacetamide-inhibited cysteine proteinase activity) on irinotecan-induced intestinal mucositis, a serious adverse effect of this medicine for the treatment of cancer. METHODS: LP-PII-IAA is composed of closely related isoforms (90%) of peptidases derived from catalysis and an osmotin protein (5%). Animals receiving co-administration of LP-PII-IAA presented a significant decrease in mortality, absence of diarrhea, histological preservation, and normalization of intestinal functions. RESULTS: Clinical homeostasis was accompanied by a reduction in MPO activity and declined levels of IL-1ß, IL-6 and KC, while the IL-10 level increased in LP-PII-IAA-treated animals. COX-2 and NF-kB immunostaining was reduced and the levels of oxidative markers (GSH, MDA) were normalized in animals that received LP-PII-IAA. CONCLUSION: We suggest that peptidases from the latex of Calotropis procera were instrumental in the suppression of the adverse clinical and physiological effects of irinotecan.

Impact of reminder on medication adherence: a structural equation model, based on study in Sikkim, India

The problem of medication non-adherence has persisted over decades. The rate of adherence decreases with time and improvement in health condition. When patients cannot follow their prescribed medication regime, it leads to deterioration of their health condition and increases their financial costs. This research aims to find the effect of reminder on medication adherence behaviour of patients when "Acceptance of Side Effect", "Quality of Life" and "Medication Beliefs" act as mediators. The sample size of the research was 505. Sampling units comprised patients suffering from different diseases in Central Referral Hospital, Sikkim, India. By developing a Structural Equation Model, the effect of reminder on the mediators and adherence was analysed. The results show a significant positive association between reminder and the three mediators. Reminder has a significant positive effect on adherence (ß=0.637, e=0.055, p=0.001). The effect is higher in the presence of mediators (ß=0.7, e=0.037, p=0.001).

Machine learning prediction of side effects for drugs in clinical trials.

Early and accurate detection of side effects is critical for the clinical success of drugs under development. Here, we aim to predict unknown side effects for drugs with a small number of side effects identified in randomized controlled clinical trials. Our machine learning framework, the geometric self-expressive model (GSEM), learns globally optimal self-representations for drugs and side effects from pharmacological graph networks. We show the usefulness of the GSEM on 505 therapeutically diverse drugs and 904 side effects from multiple human physiological systems. Here, we also show a data integration strategy that could be adopted to improve the ability of side effect prediction models to identify unknown side effects that might only appear after the drug enters the market.

Multiple cutaneous telangiectasias after the use of trastuzumab: a case report

We aim to report a particular case of cutaneous telangiectasias on the arms after immunotherapy with trastuzumab plus paclitaxel to treat breast cancer. New oncology therapies reflect a major advance in cancer treatment. They greatly increase survival; however, they still cause certain adverse cutaneous events that should be taken into account for their proper management.

Partial corneal recovery following selective trabeculoplasty-induced keratopathy: Longitudinal analysis through scheimpflug imaging.

PURPOSE: To report an uncommon case of hyperopic shift and corneal haze, flattening and thinning following a single session of selective laser trabeculoplasty (SLT), and provide longitudinal clinical data and serial analyses of corneal profile through Scheimpflug imaging. Furthermore, a careful literature review was undertaken to determine possible risk factors for this complication. OBSERVATIONS: A 47-year-old woman presented with blurred vision and mild corneal edema and haze three days following routine SLT. Ten days later, corneal edema resolved, but she was still symptomatic. Refraction exam revealed a significant hyperopic shift and high astigmatism (+4.00-6.00 x 80° versus -11.50 -0.75 x 170° at baseline). Scheimpflug imaging revealed a partial collapse of the corneal architecture, with an expressive central cornea flattening (>10 diopters) and thinning (>190µm). Over six months, refractometric and corneal parameters gradually (but not completely) returned to their pre-operative values. CONCLUSIONS AND IMPORTANCE: This tetrad of clinical findings - hyperopic shift, corneal haze, flattening and thinning - following SLT is referred herein by the authors as selective trabeculoplasty-induced keratopathy (STIK), which is a rare but serious complication. A critical analysis based on this case findings and on the few others reported so far suggests high-myopic patients to be more predisposed to this complication, as all reported cases had -5.0 diopters or more. Future studies are warranted to determine whether this complication can be prevented.

Causality assessment of adverse drug reactions by applying a global introspection method in a high complexity hospital.

Background: Causality assessment of adverse drug reactions (ADRs) is an essential approach in pharmacovigilance. The World Health Organization-Uppsala Monitoring Center (WHO-UMC) system has been considered one of the most adequate method for establishing causal relationship in hospitalized patients. Objective: To describe the causality of potential ADRs in hospitalized patients assessed by the WHO-UMC system and by different healthcare professionals. Methods: Three healthcare professionals, with different backgrounds, acted as judges to adjudicate the causality categories for potential ADRs according to WHO-UMC system, in a Brazilian high complexity hospital. Judges' agreement was evaluated by using Fleiss' and Cohen's kappa coefficients. Results: Ninety potential ADRs identified in 300 participants were adjudicated by each judge, comprising a total of 270 assessments. Most potential ADRs were classified as probable or possible (77.8%). Fleiss´ kappa revealed slight concordance among judges (k = 0.096;CI:95%;0.01-0.18). Conclusions: Diverse backgrounds may have influenced the results for causality assessment of ADRs by employing the WHO-UMC system. Despite the slight concordance found for the method, this result suggests potential opportunity to enrich the ADRs management by engaging multiprofessional teams in the process. Further studies should be considered to investigate the performance of methods for ADRs assessment in hospitalized patients in low- and middle-income countries.

Insights in Chloroquine Action: Perspectives and Implications in Malaria and COVID-19.

Malaria is a threat to human mankind and kills about half a million people every year. On the other hand, COVID-19 resulted in several hundred thousand deaths since December 2019 and remains without an efficient and safe treatment. The antimalarials chloroquine (CQ) and its analog, hydroxychloroquine (HCQ), have been tested for COVID-19 treatment, and several conflicting evidence has been obtained. Therefore, the aim of this review was to summarize the evidence regarding action mechanisms of these compounds against Plasmodium and SARS-CoV-2 infection, together with cytometry applications. CQ and HCQ act on the renin angiotensin system, with possible implications on the cardiorespiratory system. In this context, flow and image cytometry emerge as powerful technologies to investigate the mechanism of therapeutic candidates, as well as for the identification of the immune response and prognostics of disease severity. Data from the large randomized trials support the conclusion that CQ and HCQ do not provide any clinical improvements in disease severity and progression of SARS-CoV-2 patients, as well as they do not present any solid evidence of increased serious side effects. These drugs are safe and effective antimalarials agents, but in SARS-CoV-2 patients, they need further studies in the context of clinical trials. © 2020 International Society for Advancement of Cytometry.

Relationship between serum lithium concentration and kidney damage in a preclinical model.

OBJECTIVES: The aim of the present study was to assess whether there is a relationship between serum lithium concentrations and the magnitude of kidney damage in a preclinical model. METHODS: Thirty Wistar male rats were randomized into three groups: control group fed ad libitum powered standard diet for 3 months; and experimental groups fed ad libitum the same diet supplemented with 30 or 60 mmol/kg diet for 3 months (LowLi and HighLi groups respectively). Laboratory parameters were assessed at months 1 and 3 and histopathological changes were evaluated after 3 months. RESULTS: Serum lithium levels in experimental rats were within therapeutic range used in humans throughout the entire experiment. After 3 months of treatment, lithium levels were statistically higher in HighLi group. Rats of the LowLi group showed dilation of cortical tubules although with similar clearance of creatinine. Rats from the HighLi group had greater histopathological damage in addition to lower creatinine clearance than the other two groups. CONCLUSIONS: Our study suggests that during long-term treatments, even with serum lithium levels within the therapeutic range used in humans, the risk of kidney damage could increase proportionally to the serum lithium concentration.

Tumor safety and side effects of photobiomodulation therapy used for prevention and management of cancer treatment toxicities. A systematic review.

Photobiomodulation therapy (PBMT), also known as low-level laser therapy (LLLT), has been increasingly used for the treatment of toxicities related to cancer treatment. One of the challenges for the universal acceptance of PBMT use in cancer patients is whether or not there is a potential for the light to stimulate the growth of residual malignant cells that evaded oncologic treatment, increasing the risk for tumor recurrences and development of a second primary tumor. Current science suggests promising effects of PBMT in the prevention and treatment of breast cancer-related lymphedema and oral mucositis, among other cancer treatment toxicities. Nevertheless, this seems to be the first systematic review to analyze the safety of the use of PBMT for the management of cancer-related toxicities. Scopus, MEDLINE/PubMed, and Embase were searched electronically. A total of 27 articles met the search criteria. Selected studies included the use of PBMT for prevention and treatment of oral mucositis, lymphedema, radiodermatitis, and peripheral neuropathy. Most studies showed that no side effects were observed with the use of PBMT. The results of this systematic review, based on current literature, suggest that the use of PBMT in the prevention and management of cancer treatment toxicities does not lead to the development of tumor safety issues.

Responsabilidad penal médica: consideraciones en la aplicación del principio del doble efecto / Medical Criminal Liability: considerations in the application of the principle of double effect

La responsabilidad médica en Chile contempla un espacio de discrecionalidad, en situaciones de peligro para la mujer durante el embarazo y en el tratamiento paliativo de pacientes terminales. En estos casos se presentan conceptos jurídicos indeterminados, en el ordenamiento jurídico chileno, que requieren de una propuesta interpretativa en consonancia con la protección del derecho a la vida, en actividades médicas que tengan por efecto colateral la muerte de personas inocentes (AU).

The chilean medical liability leaves a room of discretion in cases when a hazardous condition exists during the pregnancy or palliative care for those dying from a terminal disease. In such cases, the Chilean legal system presents undefined legal concepts. This concepts need to be in accordance with the promotion of the constitutional right to life, in medical cases where innocent people could die by side effect (AU).

Responsabilidad penal médica: consideraciones en la aplicación del principio del doble efecto / Medical Criminal Liability: considerations in the application of the principle of double effect

La responsabilidad médica en Chile contempla un espacio de discrecionalidad, en situaciones de peligro para la mujer durante el embarazo y en el tratamiento paliativo de pacientes terminales. En estos casos se presentan conceptos jurídicos indeterminados, en el ordenamiento jurídico chileno, que requieren de una propuesta interpretativa en consonancia con la protección del derecho a la vida, en actividades médicas que tengan por efecto colateral la muerte de personas inocentes (AU).

The chilean medical liability leaves a room of discretion in cases when a hazardous condition exists during the pregnancy or palliative care for those dying from a terminal disease. In such cases, the Chilean legal system presents undefined legal concepts. This concepts need to be in accordance with the promotion of the constitutional right to life, in medical cases where innocent people could die by side effect (AU).

Walking hyponatremia syndrome of inappropriate antidiuretic hormone secretion secondary to carbamazepine use: a case report.

BACKGROUND: Severe hyponatremia is rare when carbamazepine is used as monotherapy. It is common to encounter this imbalance in the hospital setting, but rare in the ambulatory one. Here, we present a case of hyponatremia secondary to carbamazepine use in an otherwise asymptomatic patient. CASE PRESENTATION: A 44-year-old Guatemalan woman presented to our outpatient clinic with a chief complaint of left knee pain. One month prior, our patient had previously consulted with an outside physician, who prescribed her with 300 mg of carbamazepine, 5 mg of prednisone every 24 hours, and ibuprofen every 8 hours as needed. The symptoms did not resolve and our patient had increased the dose to 600 mg of carbamazepine and 20 mg of prednisone 7 days prior. Our patient complained of left knee pain, fatigue, and bilateral lower limb cramps. No pertinent medical history was recorded and her vital signs were within normal limits. A physical examination was non-contributory, only multiple port-wine stains in the upper and lower extremities associated with mild hypertrophy of the calves, more prominent on the right side. Laboratory studies revealed: a serum sodium level of 119 mmol/L, potassium level of 2.9 mmol/L, thyroid-secreting hormone of 1.76 mIU/m, thyroxine of 14.5 ng/dL, and serum osmolality at 247 mmol/kg. No neurologic or physical disabilities were recorded. In the emergency department, her electrolyte imbalance was corrected and other diagnostic studies revealed: a urinary sodium level of 164 mmol/L and osmolality at 328 mmol/kg. Our patient was diagnosed with syndrome of inappropriate antidiuretic hormone secretion secondary to carbamazepine use, hypokalemia secondary to corticosteroid therapy, and Klippel-Trénaunay-Weber syndrome. Carbamazepine was discontinued, fluid restriction ordered, and hypokalemia was corrected. One week after discharge, our patient no longer felt fatigued, the cramps were not present, and her left knee pain had mildly improved with acetaminophen use and local nonsteroidal anti-inflammatory cream. Electrolyte studies revealed a sodium level of 138 mmol/L, potassium level of 4.6 mmol/L, and serum osmolality at 276 mmol/L. CONCLUSIONS: Hyponatremia can be misdiagnosed if not recognized promptly; suspicion should be high when risk factors are present and the patient has been prescribed antiepileptic drugs. Presence of mild symptoms such as fatigue or dizziness should lead to suspicion and subsequent laboratory testing. Patients can suffer from neurologic complications if the imbalance is not corrected.

The impact of preapheresis white blood cell count on autologous peripheral blood stem cell collection efficiency and HSC infusion side effect rate.

BACKGROUND: Autologous peripheral blood hematopoietic stem cell (PBSC) collection efficiency (CE) is reportedly affected by the patient's blood properties; however, studies to identify factors correlated with CE have shown inconsistent results. Additionally, variables such as stem cell graft granulocyte content and patient age, sex, and underlying disease, may be associated with hematopietic stem cell (HSC) infusion-related adverse reactions. In this study, we evaluated the correlation of preleukapheresis PB granulocyte count and PBSC harvest variables with CD34+ collection yield and efficiency, and thawed HSC infusion side effect occurrence. PATIENTS AND METHODS: We evaluated data from 361 patients who had undergone autologous PBSC transplant. Large volume leukapheresis was the method for PBSC collection. Complete Blood Count and CD34+ cell enumeration were performed in the preapheresis PB and the apheresis product sample. The PBSC grafts were submitted to non-controlled rate freezing after addition of 5% DMSO plus 6% hidroxyethylstarch as a cryoprotectant solution. The cryopreserved graft was thawed in a 37°C water bath and then infused without further manipulation. RESULTS: The CD34+ yield was associated with preapheresis PB CD34+ count and immature granulocyte count. The PBSC CE was negatively correlated with preapheresis white blood cell (WBC), immature granulocyte and granulocyte count. The leukapheresis product total nucleated cell (TNC) and granulocyte content was correlated with the thawed graft infusion side effect occurrence. CONCLUSION: This study has shown that preapheresis PB WBC and granulocyte counts were associated with leukapheresis CE. Additionally, the leukapheresis product TNC and granulocyte content was correlated with thawed graft infusion side effect occurrence.

Pharmacology and Toxicology of Polyphenols with Potential As Neurotropic Agents in Non-communicable Diseases.

BACKGROUND: The central nervous system (CNS) is involved in organic integration. Nervous modulation via bioactive compounds can modify metabolism in order to prevent systemic noncommunicable diseases (NCDs). Concerning this, plant polyphenols are proposed as neurotropic chemopreventive/ therapeutic agents, given their redox and regulating properties. OBJECTIVE: To review polyphenolic pharmacology and potential neurological impact on NCDs. METHOD: First, polyphenolic chemistry was presented, as well as pharmacology, i.e. kinetics and dynamics. Toxicology was particularly described. Then, functional relevance of these compounds was reviewed focusing on the metabolic CNS participation to modulate NCDs, with data being finally integrated. RESULTS: Oxidative stress is a major risk factor for NCDs. Polyphenols regulate the redox biology of different organic systems including the CNS, which participates in metabolic homeostasis. Polyphenolic neurotropism is determined by certain pharmacological characteristics, modifying nervous and systemic physiopathology, acting on several biological targets. Nonetheless, because these phytochemicals can trigger toxic effects, they should not be recommended indiscriminately. CONCLUSION: Summing up, the modulating effects of polyphenols allow for the physiological role of CNS on metabolism and organic integration to be utilized in order to prevent NCDs, without losing sight of the risks.

Prevalence, patterns, and perceived value of complementary and alternative medicine among cancer patients: a cross-sectional, descriptive study.

BACKGROUND: Sophisticated conventional medicine (CM) has brought significant advances to cancer prevention, detection, and treatment. However, many cancer patients still turn to complementary and alternative medicine (CAM) treatment. This study explored the prevalence, patterns, and perceived value of CAM among cancer patients. METHODS: This quantitative descriptive study was conducted between March 1, 2015, and July 31, 2015, among a cross-sectional, convenience sample of patients from the Oncology Department of San Fernando General Hospital in Trinidad and Tobago. Face-to-face interviews were conducted at the oncology clinic and treatment suite after obtaining informed consent. Data analysis included descriptive analysis, chi-square tests, and binary logistic regression analysis. RESULTS: The prevalence of CAM use among a sample of 350 cancer patients was 39.1% (39.6% for breast cancer, 44.4% for prostate cancer, 37% for ovarian cancer, and 38.7% for colon cancer patients). Herbs were the most common type of CAM used (93.4%), followed by spiritual therapy (73.7%). CAM use was more prevalent among females (68.6%), Indo-Trinidadians (63.5%), and patients aged 41-50 years (37.2%). The majority (70%-80%) rated CAM efficacy on perceived value. CAM was used mainly because of a desire to try anything that might help (67.6%), followed by it being congruent with the patients' beliefs (59.1%). Patients knew about CAM mainly through friends (69.3%) and family (69.3%). Most patients were generally satisfied (93.6%) and considered CAM helpful (89.8%), but the majority never informed their health care provider of CAM use (78.8%). Patients reported the simultaneous use of more than one type of CAM, without considering or knowing of possible side-effects. The perceived value of CAM included empowerment, control, cure, and improved quality of life. CAM use was associated with age, but no predictors of CAM use could be identified. CONCLUSION: Medicinal herbs and spiritual therapy are commonly used among cancer patients because of perceived benefits and satisfaction. CAM use is more prevalent among females, Indo-Trinidadians, and patients aged 41-50 years old. There are no useful predictors of CAM use. More than one type of CAM is commonly used simultaneously without disclosure to health care providers.