Cluster analysis of patient characteristics, treatment modalities, renal impairments, and inflammatory markers in diabetes mellitus.

Type 2 diabetes mellitus (T2DM) is caused by an interplay of various factors where chronic hyperglycemia and inflammation have central role in its onset and progression. Identifying patient groups with increased inflammation in order to provide more personalized approach has become crucial. We hypothesized that grouping patients into clusters according to their clinical characteristics could identify distinct unique profiles that were previously invisible to the clinical eye. A cross-sectional record-based study was performed at the Primary Health Care Center Podgorica, Montenegro, on 424 T2DM patients aged between 30 and 85. Using hierarchical clustering patients were grouped into four distinct clusters based on 12 clinical variables, including glycemic and other relevant metabolic indicators. Inflammation was assessed through neutrophil-to-lymphocyte (NLR) and platelet to lymphocyte ratio (PLR). Cluster 3 which featured the oldest patients with the longest T2DM duration, highest hypertension rate, poor glycemic control and significant GFR impairment had the highest levels of inflammatory markers. Cluster 4 which featured the youngest patients, with the best glycemic control, the highest GFR had the lowest prevalence of coronary disease, but not the lowest levels of inflammatory markers. Identifying these clusters offers physicians opportunity for more personalized T2DM management, potentially mitigating its associated complications.

Priapism associated with anti-seizure medications: a pharmacovigilance study and a review of published cases.

BACKGROUND: Recently, case reports of priapism associated with the use of some anti-seizure medications began to emerge in the literature. We aimed to investigate if there is a potential safety signal of priapism among individual anti-seizure medications and to search the literature for relevant published cases. RESEARCH DESIGN AND METHODS: We conducted a disproportionality analysis using OpenVigil 2.1 to query the United States Food and Drug Administration's Adverse Event Reporting System (FAERS) database. Literature search was conducted in PubMed/MEDLINE, Scopus and Web of Science up to 12 July 2023. RESULTS: We identified positive signal of priapism for valproic acid and its derivatives (n = 23, chi-squared = 59.943, PRR = 4.566), gabapentin (n = 20, chi-squared = 9.790, PRR = 2.060), lamotrigine (n = 16, chi-squared = 8.318, PRR = 2.120), levetiracetam (n = 16, chi-squared = 10.766, PRR = 2.329), topiramate (n = 14, chi-squared = 28.067, PRR = 3.972) and carbamazepine (n = 8, chi-squared = 6.147, PRR = 2.568), as well as published cases of priapism associated with these drugs. We also found published cases of priapism for pregabalin and phenytoin in the literature and FAERS, and at least one reported adverse event of priapism in FAERS for clonazepam, lacosamide, ethosuximide, oxcarbazepine, and vigabatrin in which they were considered primary suspect. CONCLUSIONS: Our study identified signals for priapism for several anti-seizure medications, but these results need to be confirmed in well-designed pharmacoepidemiological studies.

Bioequivalence of Different Formulations of Zonisamide Oral Suspensions: A Short Review.

To satisfy the needs of pediatric and other patients with focal onset seizures who cannot swallow solid dosage forms of zonisamide, an oral liquid form of this drug is necessary in clinical practice. Although there are two oral suspensions of zonisamide with marketing authorization (MA), there are issues of availability and high cost which limit their use and inspire extemporaneous compounding. Extemporaneously compounded oral suspensions of zonisamide are prepared according to different formulas and vary in stability; therefore it is essential to test this characteristic. Bioequivalence of extemporaneously compounded oral suspensions has never been tested, and the efficacy and safety of zonisamide oral suspensions have generally not been demonstrated in clinical trials. As a narrow therapeutic window drug, zonisamide requires precision in dosing, which could be achieved only with dosage forms with established bioavailability, efficacy, and safety. In order to avoid underdosing and toxicity with zonisamide oral suspensions and utilize their full therapeutic potential, it is necessary to perform bioequivalence studies with each variation of extemporaneously compounded oral suspension and also clinical trials with both commercial and extemporaneous oral suspensions of zonisamide.

Factors associated with gastrointestinal dysmotility in critically ill patients.

Critical illness may disrupt nutritional, protective, immune, and endocrine functions of the gastrointestinal tract, leading to a state of gastrointestinal dysmotility. We aimed to identify factors associated with the occurrence of gastrointestinal dysmotility in critically ill patients. A cross-sectional retrospective study was conducted, using patient files as a source of data. The study included 185 critically ill patients treated in the intensive care unit of the University Clinical Center, Kragujevac, Serbia, from January 1, 2016, to January 1, 2022. Significant risk factors associated with some form of gastrointestinal dysmotility were acute kidney injury (with paralytic ileus, nausea, vomiting, and constipation), recent abdominal surgery (with ileus, nausea, vomiting, and constipation), mechanical ventilation (with ileus, and nausea), age (with ileus and constipation), and use of certain medication such as opioids (with ileus, gastro-esophageal reflux, nausea, vomiting, and constipation), antidepressants (with ileus, nausea, and vomiting), and antidiabetics (with ileus). On the other hand, Charlson comorbidity index had divergent effects, depending on the form of gastrointestinal dysmotility: it increased the risk of gastro-esophageal reflux but protected against ileus, nausea, and vomiting. In clonclusion, recognition of factors associated with gastrointestinal dysmotility should initiate preventative measures and, thus, accelerate the recovery of critically ill.

The efficacy of lapatinib in patients with metastatic HER2 positive breast cancer who received prior therapy with monoclonal antibodies and antibody-drug conjugate: a single institutional experience.

The choice of the anti-HER2 agent depends on country-specific availability, the specific, previously administered anti-HER2 therapy and the relapse-free interval, although there is not much published data on the use of lapatinib after progression on pertuzumab and/or T-DM1. The aim of this research is to determine efficacy of lapatinib in this setting. This research included 111 patients with metastatic HER2 positive breast cancer who received lapatinib with capecitabine at The Oncology Institute of Vojvodina. Lapatinib was given to 83 patients after trastuzumab without prior exposure to pertuzumab or T-DM1 while 28 patients received lapatinib after prior exposure to trastuzumab, pertuzumab and/or T-DM1. In order to determine efficacy of lapatinib in both groups, we measured progression free survival (PFS) and overall survival (OS), as well as by subsets: hormonal status (ER-positive and/or PR-positive tumours versus ER-negative and PR-negative tumours), the number of positive axillary lymph nodes (four or more positive axillary lymph nodes versus less than four positive axillary lymph nodes), marker of proliferation (Ki-67 ≥ 30 versus Ki-67 < 30), disease free interval (metastatic recurrence ≤ 1 year after initial diagnosis versus metastatic recurrence > 1 year after initial diagnosis or de novo metastatic disease. Median PFS was 5.6 months (95% CI 4.6-6.6) in the group of patients who received lapatinib after prior exposure to trastuzumab, pertuzumab and/or T-DM 1 and 7.4 months (95% CI 6.1-10.2) in the group of patients who received lapatinib after trastuzumab (HR, 0.79; 95% CI 0.61-0.98; P = 0.09). The patients with negative prognostic factors such as hormone receptor negativity, more than four positive axillary lymph nodes, marker of proliferation Ki 67 ≥ 30 and metastatic recurrence ≤ 1 year after initial diagnosis, had a similar PFS, regardless of receiving lapatinib after prior exposure to trastuzumab, pertuzumab and/or T-DM1 or without prior exposure. Median OS was 10.1 months (95% CI 8.6-NR) in the group that received lapatinib after exposure to trastuzumab, pertuzumab and/or T-DM1 and 16.3 months (95% CI 14.4-20.2) in the group of patients who received lapatinib after trastuzumab (HR, 0.76; 95% CI, 0.59-0.94; P = 0.04). Patients with negative prognostic factors such as hormone receptor negativity, more than four positive axillary lymph nodes and marker of proliferation Ki 67 ≥ 30, had no distinctly worse OS, regardless of receiving lapatinib after prior exposure to trastuzumab, pertuzumab and/or T-DM1 or without prior exposure. Lapatinib with capecitabine is an effective therapeutic option, especially in patients with negative prognostic factors, who have received prior chemotherapy, trastuzumab, pertuzumab, T-DM1 and remains an acceptable option for HER2 positive metastatic breast cancer until the novel drugs are approved in developing countries.

COVID-19 vaccines and cancer patients: acceptance, attitudes and safety.

PURPOSE: Recommendations and guidelines consider cancer patients a high-priority population for COVID-19 immunization. Vaccination process in Serbia began in January 2021 with four available vaccines. We have conducted a cross-sectional study investigating cancer patients' acceptability of anti SARS-COV2 vaccines. METHODS: The study included 767 patients with solid and hematologic malignancies treated at the Oncology Institute of Vojvodina, Serbia. During July and August 2021 patients filled in an individual paper questionnaire on anti SARS-COV2 vaccination acceptance, preferences, side effects and information origin. Data on treatment phase, diagnosis and treatment was collected from electronic health records. RESULTS: During the first six months of vaccination campaign in Serbia 41% (320/767) of the investigated oncology patients received COVID-19 vaccines. The median age of vaccinated patients was 65 years (28-84). Most of them (75%) were in active treatment of cancer. Half of the unvaccinated patients (52%) wish to get vaccinated after the end of their cancer treatment. Around 10% of the patients definitely refused vaccination. The majority of information on COVID-19 vaccines cancer patients got from their oncologist, television and newspapers. Side effects were reported by 10.93% of the patients after the first dose and 13,31% after the second dose. No serious side effects were reported. CONCLUSION: We have confirmed that patients are reluctant of receiving vaccine due to fear of side effects, especially during the active cancer treatment. However, real-world evidence and clinical trials data have gathered enough evidence to reassure any doubts of the patients and their oncologists on safety and efficacy of anti SARS-COV2 vaccines.

Exogenous putrescine affects polyamine and arginine metabolism in rat liver following bile ductus ligation.

Rat bile duct ligation (BDL) represents a useful method that mimics obstructive extrahepatic cholestasis, which is known to be a frequent disorder in humans. Polyamines (putrescine, spermidine, and spermine) are one of the key molecules regulating cell proliferation and differentiation. This work aimed to evaluate the potential beneficial properties of putrescine in rat BDL model by studying several biochemical parameters reflecting liver function and polyamine metabolism. Rats that were subjected to BDL were injected with putrescine (150 mg/kg) for 9 days, while in parallel another group with BDL remained untreated. Two control groups were included as well, sham-opened and putrescine-treated group. The following plasma parameters: ALT, AST, γ-GT, ALP, bilirubin, bile acids, as well as liver malondialdehyde and polyamine concentration and the activity of enzymes involved in polyamine metabolism were studied. After BDL, significant alterations in plasma biochemical parameters occurred, where a 9-day putrescine treatment significantly alleviated liver function deterioration. Putrescine also increased liver polyamines' concentrations and polyamine and diamine oxidase activities in rats submitted to BDL. Our results demonstrated, for the first time, that putrescine plays an important role in preserving liver tissue function in rats with experimentally induced cholestasis.

Unusual metastasis of esophageal cancer.

INTRODUCTION: Carcinoma of the esophagus is in the eighth place by the frequency of malignant diseases and the sixth cause of death from cancer worldwide. It usually metastasizes to regional lymph nodes, liver, lungs, central nervous system, and bones, but metastases can appear to unusual locations such as facial skin and lips. CASE REPORT: We presented a 56- year-old man who reported to his physician because of upper lip swelling. A physical checkup of the patients also showed a lesion on the skin of the left temporal region and both lesions were biopsied. Based on the results of histopathological and immunohistochemical analyses of the samples a diagnosis of metastatic adenocarcinoma to the skin was established. Additional diagnostic procedures, including esophagogastroduodenoscopy, detected the infiltration into the distal part of esophagus, which was histopathologically confirmed as adenocarcinoma of esophagus. The results of positron emission tomography/computed tomography (PET/CT) examination showed the invasion of the disease. Because of the disease expansion, a multidisciplinary oncology team suggested chemo- and radiotherapy treatment. The patient has received 4 cycles of platinum-based chemotherapy so far. CONCLUSION: The physicians should always consider unusual skin lesions as the first sign of cancer spreading.

Universal impulse noise filter based on genetic programming.

In this paper, we present a novel method for impulse noise filter construction, based on the switching scheme with two cascaded detectors and two corresponding estimators. Genetic programming as a supervised learning algorithm is employed for building two detectors with complementary characteristics. The first detector identifies the majority of noisy pixels. The second detector searches for the remaining noise missed by the first detector, usually hidden in image details or with amplitudes close to its local neighborhood. Both detectors are based on the robust estimators of location and scale-median and MAD. The filter made by the proposed method is capable of effectively suppressing all kinds of impulse noise, in contrast to many existing filters which are specialized only for a particular noise model. In addition, we propose the usage of a new impulse noise model-the mixed impulse noise, which is more realistic and harder to treat than existing impulse noise models. The proposed model is the combination of commonly used noise models: salt-and-pepper and uniform impulse noise models. Simulation results show that the proposed two-stage GP filter produces excellent results and outperforms existing state-of-the-art filters.