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Diagnostics (Basel, Switzerland) Mar 2024Patients with immune-mediated rheumatic disease-related calcinosis comprise a subgroup at risk of encountering a more severe clinical outcome. Early assessment is...
Patients with immune-mediated rheumatic disease-related calcinosis comprise a subgroup at risk of encountering a more severe clinical outcome. Early assessment is pivotal for preventing overall disease progression, as calcinosis is commonly overlooked until several years into the disease and is considered as a 'non-lethal' manifestation. This single-center retrospective study explored the prevalence, clinical associations, and impact on survival of subcutaneous calcinosis in 86 patients with immune-mediated rheumatic diseases (IMRD). Calcinosis predominantly appeared in individuals with longstanding disease, particularly systemic sclerosis (SSc), constituting 74% of cases. Smaller calcinosis lesions (≤1 cm) were associated with interstitial lung disease, musculoskeletal involvement, and digital ulcerations, while larger lesions (≥4 cm) were associated with malignancy, severe peripheral artery disease, and systemic arterial hypertension. The SSc calcinosis subgroup exhibited a higher mean adjusted European Scleroderma Study Group Activity Index score than those without. However, survival rates did not significantly differ between the two groups. Diltiazem was the most commonly used treatment, and while bisphosphonates reduced complications related to calcinosis, complete resolution was not achieved. The findings underscore current limitations in diagnosing, monitoring, and treating calcinosis, emphasizing the need for further research and improved therapeutic strategies to improve patient care and outcomes.
PubMed: 38535057
DOI: 10.3390/diagnostics14060637 -
Hypertension in Pregnancy Dec 2024Preeclampsia (PE) is a pregnancy disorder that represents a major cause of maternal and perinatal morbidity and mortality. (Meta-Analysis)
Meta-Analysis
BACKGROUND
Preeclampsia (PE) is a pregnancy disorder that represents a major cause of maternal and perinatal morbidity and mortality.
METHODS
This network meta-analysis was registered with PROSPERO. We searched the PubMed, ClinicalTrials.gov. and Embase databases for studies published from inception to the 31 of March 2023. RevMan5.3 software provided by the Cochrane Collaboration was used for direct meta-analysis (DMA) statistical analysis. Funnel maps, network meta-analysis (NMA), the surface under the cumulative ranking curve (SUCRA) to rank the different interventions and publication bias were generated by STATA 17.0 software.
RESULTS
We included eight randomized controlled trials (RCTs) involving a total of 1192 women with PE; two studies were of high quality and six were of moderate quality. Eight interventions were addressed in the NMA. In the DMA, we found that blood pressure in the Ketanserin group were significantly higher than those in the Nicardipine group. NMA showed that blood pressure in the Dihydralazine group was significantly higher than that in the Methyldopa, Labetalol, Nicardipine and Diltiazem groups. And the blood pressure in the Labetalol group was significantly lower than that in the Nicardipine group. SUCRA values showed that Diltiazem was more effective in lowering blood pressure than other drugs looked at in this study.
CONCLUSION
According to the eight RCTs included in this study, Diltiazem was the most effective in reducing blood pressure in PE patients; Labetalol and Nicardipine also had good effects. Diltiazem is preferred for the treatment of patients with severe PE and high blood pressure.
Topics: Pregnancy; Female; Humans; Antihypertensive Agents; Labetalol; Pre-Eclampsia; Diltiazem; Nicardipine; Network Meta-Analysis
PubMed: 38488570
DOI: 10.1080/10641955.2024.2329068 -
Journal of Pharmacological Sciences Apr 2024Platelet-activating factor (PAF) is expected to increase esophageal motility. However, to the best of our knowledge, this has not been examined. Thus, we investigated...
Platelet-activating factor (PAF) is expected to increase esophageal motility. However, to the best of our knowledge, this has not been examined. Thus, we investigated the contractile effects of PAF on guinea pig (GP) esophageal muscularis mucosae (EMM) and the extracellular Ca influx pathways responsible. PAF (10-10 M) contracted EMM in a concentration-dependent manner. PAF (10 M)-induced contractions were almost completely suppressed by apafant (a PAF receptor antagonist, 3 × 10 M). In EMM strips, PAF receptor and PAF-synthesizing/degrading enzyme mRNAs were detected. PAF (10 M)-induced contractions were abolished by extracellular Ca removal but were not affected by diltiazem [a voltage-dependent Ca channel (VDCC) inhibitor, 10 M]. PAF (10 M)-induced contractions in the presence of diltiazem were significantly suppressed by LOE-908 [a receptor-operated Ca channel (ROCC) inhibitor, 3 × 10 M], SKF-96365 [an ROCC and store-operated Ca channel (SOCC) inhibitor, 3 × 10 M], and LOE-908 plus SKF-96365. Among the tested ROCC/SOCC-related mRNAs, Trpc3, Trpc6, and Trpv4/Orai1, Orai3, and Stim2 were abundantly expressed in EMM strips. These results indicate that PAF potently induces GP EMM contractions that are dependent on extracellular Ca influx through ROCCs/SOCCs, and VDCCs are unlikely to be involved.
Topics: Guinea Pigs; Animals; Diltiazem; Platelet Activating Factor; Acetamides; Calcium Channels; Mucous Membrane; Calcium; Isoquinolines
PubMed: 38485343
DOI: 10.1016/j.jphs.2024.01.009 -
Journal of Medical Case Reports Mar 2024Ischemia with non-obstructive coronary artery disease is a prevalent form of ischemic heart disease. The majority of ischemia with non-obstructive coronary artery...
BACKGROUND
Ischemia with non-obstructive coronary artery disease is a prevalent form of ischemic heart disease. The majority of ischemia with non-obstructive coronary artery disease cases are attributed to underlying factors such as coronary microvascular dysfunction (CMD) and/or coronary artery spasm. Ischemia with non-obstructive coronary artery disease can present with various clinical manifestations. Recurrent syncope is an atypical complaint in patients with ischemia with non-obstructive coronary artery disease.
CASE PRESENTATION
This case report describes the presentation of a 58-year-old Chinese male patient who experienced repeated episodes of syncope. The syncope was found to be caused by concomitant coronary artery spasm and presumptive coronary microvascular dysfunctionc suggested by "slow flow" on coronary angiography. The patient was prescribed diltiazem sustained-release capsules, nicorandil, and atorvastatin. During the three-month follow-up conducted on our outpatient basis, the patient did not experience a recurrence of syncope.
CONCLUSION
This study highlights the importance of considering ischemia with non-obstructive coronary artery disease as a potential cause of syncope in the differential diagnosis. It emphasizes the need for early diagnosis of ischemia with non-obstructive coronary artery disease to facilitate more effective management strategies.
Topics: Male; Humans; Middle Aged; Coronary Artery Disease; Coronary Vasospasm; Myocardial Ischemia; Coronary Angiography; Syncope; Ischemia; Coronary Vessels
PubMed: 38468268
DOI: 10.1186/s13256-023-04316-y -
Cureus Feb 2024Background The elderly population differs from adults in having various physiological changes and multiple diseases, which demand the use of multiple medications. The...
Retrospective Analysis of Potential Adverse Drug Interactions in the Drugs Prescribed to the Elderly at a Tertiary Health Care Center in Raipur, Chhattisgarh, Central India.
Background The elderly population differs from adults in having various physiological changes and multiple diseases, which demand the use of multiple medications. The practice of polypharmacy in the elderly leads to numerous harmful effects like adverse drug reactions, adverse drug-drug interactions (DDIs), poor compliance, etc. Methodology This study collected 295 case files of elderly patients retrospectively in the Departments of General Medicine, Cardiology and Nephrology after obtaining Institute Ethics Committee approval to look for the potential adverse DDIs with their severity according to the clinical significance. Results and interpretation The total number of adverse DDIs identified was 156, the maximum in Category 'C.' Salbutamol plus carvedilol/propranolol, ramipril plus telmisartan and ivabradine plus diltiazem were the adverse DDIs categorized under severity 'X'. The identified DDIs were categorised according to the mechanism such as increased bleeding risk, hypokalemia, hyperkalaemia, reduced effect of drugs and increased effect of drugs. Conclusion Polypharmacy can lead to several adverse consequences in the elderly, of which adverse DDIs play a crucial role in harmful health outcomes. This study brings out the significance of predicting drug interactions beforehand which can reduce the risk of bleeding and other risks of hyper/hypokalaemia, hyponatremia and hypoglycaemia.
PubMed: 38465112
DOI: 10.7759/cureus.53767 -
Cureus Jan 2024An electrocardiogram, used to not only assess the rate and rhythm of the heart but also to evaluate for injury to the heart, is performed by attaching 12 leads to the...
An electrocardiogram, used to not only assess the rate and rhythm of the heart but also to evaluate for injury to the heart, is performed by attaching 12 leads to the patient's body. A myocardial infarction can be mimicked by the misplacement of the leads. A 58-year-old man with long-distance running-associated bradycardia developed postoperative atrial fibrillation with a rapid ventricular response. He converted to normal sinus rhythm after a single oral dose of 30 milligrams of diltiazem; however, the automated reading of the electrocardiogram performed in the hospital showed new changes suggestive of a postero-lateral myocardial infarction, including Q waves in leads I and aVL, as well as early precordial R wave progression with R waves and positive T waves in V and V, and a dominant R wave (R wave to S wave ratio greater than one) in V. A cardiac work-up was entirely normal: serial troponin levels, thyroid stimulating hormone, echocardiogram, computerized tomography of the chest, and Doppler studies of the extremities. Lead misplacement during the electrocardiogram was suspected during the subsequent evaluation by an astute cardiologist; the findings were diagnostic for a left arm to right arm limb lead reversal. All the changes in myocardial infarction were absent when the electrocardiogram was repeated in the office. Misplacement of leads during an electrocardiogram is not a rare event; therefore, the clinician needs to consider the possibility of improper placement of the leads when evaluating an electrocardiogram. Indeed, emotional distress, additional diagnostic procedures, and potentially harmful procedures may be experienced by the patient from incorrect diagnoses based on electrode misplacement during an electrocardiogram; in addition, there are often increased costs to the patient and the healthcare system. Therefore, in the setting of an incorrect diagnosis attributed to lead misplacement during the performance of an electrocardiogram, the acronym MISFIT (which uses the first letters of the words "myocardial infarction simulated from improper telemetry") has been introduced. In conclusion, it is important to emphasize that a MISFIT is characterized by an electrocardiogram 'mis'diagnosis of a myocardial infarction that does not 'fit' with the clinical scenario.
PubMed: 38425620
DOI: 10.7759/cureus.53197 -
Scientific Reports Feb 2024In the past, quadratus lumborum block (QLB) was mostly used for postoperative analgesia in patients, and few anesthesiologists applied it during surgery with opioid-free... (Randomized Controlled Trial)
Randomized Controlled Trial
In the past, quadratus lumborum block (QLB) was mostly used for postoperative analgesia in patients, and few anesthesiologists applied it during surgery with opioid-free anesthesia (OFA). Consequently, it is still unclear whether QLB in the supine position can provide perfect analgesia and inhibit anesthetic stress during surgery under the OFA strategy. To observe the clinical efficacy of ultrasound-guided quadratus lumborum block (US-QLB) in the supine position with OFA for lower abdominal and pelvic surgery. A total of 122 patients who underwent lower abdominal or pelvic surgery in People's Hospital of Wanning between March 2021 and July 2022 were selected and divided into a quadratus lumborum block group (Q) (n = 62) and control group (C) (n = 60) according to the random number table method. Both groups underwent general anesthesia combined with QLB in the supine position. After sedation, unilateral or bilateral QLB was performed via the ultrasound guided anterior approach based on images resembling a "human eye" and "baby in a cradle" under local anesthesia according to the needs of the operative field. In group Q, 20 ml of 0.50% lidocaine and 0.20% ropivacaine diluted in normal saline (NS) were injected into each side. In group C, 20 ml of NS was injected into each side. The values of BP, HR, SO, SE, RE, SPI, NRS, Steward score, dosage of propofol, dexmedetomidine, and rocuronium, the number of patients who needed remifentanil, propofol, or diltiazem, puncture point, block plane, duration of anesthesia, catheter extraction, and wakefulness during the operation were monitored. There were no significant differences in the general data, number of cases requiring additional remifentanil, propofol, or diltiazem treatment, as well as puncture point and puncture plane between the two groups (P > 0.05). HR, SBP, and DBP values were higher in group Q than in group C at T1; HR, SPI, and SE, while RE values were lower in group Q than in group C at T3, SE, and RE; the Steward score was higher in group Q than in group C at T4 and T5, and the difference was statistically significant (P < 0.05). The extubation and awake times were lower in group Q than in group C, and the difference was statistically significant (P < 0.05). The SE, RE, and SPI values were lower at T1, T2, T3, and T4 than at T0. The Steward scores at T4 and T5 were higher in group Q than in group C, and were lower than at T0, with a statistically significant difference (P < 0.05). There were significant differences in the effectiveness of postoperative analgesia between the two groups at t1, t3 and t4 (P < 0.05). US-QLB in the supine position with OFA is effective in patients undergoing lower abdominal or pelvic surgery with stable intraoperative vital signs, complete recovery and better postoperative analgesia.
Topics: Humans; Analgesics, Opioid; Anesthetics, Local; Remifentanil; Propofol; Diltiazem; Supine Position; Pain, Postoperative; Nerve Block; Ultrasonography, Interventional
PubMed: 38409359
DOI: 10.1038/s41598-024-55370-5 -
Pharmaceutics Feb 2024Human serum alpha-1-acid glycoprotein (AAG) is an acute-phase plasma protein involved in the binding and transport of many drugs, especially basic and lipophilic...
Human serum alpha-1-acid glycoprotein (AAG) is an acute-phase plasma protein involved in the binding and transport of many drugs, especially basic and lipophilic substances. The sialic acid groups that terminate the N-glycan chains of AAG have been reported to change in response to numerous health conditions and may have an impact on the binding of drugs to AAG. In this study, we quantified the binding between native and desialylated AAG and seven drugs from different pharmacotherapeutic groups (carvedilol, diltiazem, dipyridamole, imipramine, lidocaine, propranolol, vinblastine) using microscale thermophoresis (MST). This method was chosen due to its robustness and high sensitivity, allowing precise quantification of molecular interactions based on the thermophoretic movement of fluorescent molecules. Detailed glycan analysis of native and desialylated AAG showed over 98% reduction in sialic acid content for the enzymatically desialylated AAG. The MST results indicate that desialylation generally alters the binding affinity between AAG and drugs, leading to either an increase or decrease in values, probably due to conformational changes of AAG caused by the different sialic acid content. This effect is also reflected in an increased denaturation temperature of desialylated AAG. Our findings indicate that desialylation impacts free drug concentrations differently, depending on the binding affinity of the drug with AAG relative to human serum albumin (HSA). For drugs such as dipyridamole, lidocaine, and carvedilol, which have a higher affinity for AAG, desialylation significantly changes free drug concentrations. In contrast, drugs such as propranolol, imipramine, and vinblastine, which have a strong albumin binding, show only minimal changes. It is noteworthy that the free drug concentration of dipyridamole is particularly sensitive to changes in AAG concentration and glycosylation, with a decrease of up to 15% being observed, underscoring the need for dosage adjustments in personalized medicine.
PubMed: 38399284
DOI: 10.3390/pharmaceutics16020230 -
Journal of Education & Teaching in... Jan 2024Emergency medicine residents and medical students on emergency medicine rotation.
AUDIENCE
Emergency medicine residents and medical students on emergency medicine rotation.
BACKGROUND
Calcium channel blocker (CCB) overdoses can be severe with potentially serious adverse outcomes. CCBs work by blocking the calcium channels on smooth and cardiac muscle tissue. At low dose ranges, dihydropyridine CCBs (such as nifedipine, amlodipine, and nicardipine) block the L-type calcium receptors in the peripheral vasculature, whereas non-dihydropyridine CCBs (such as: verapamil and diltiazem) affect the L-type calcium receptors in the myocardium.1 Because of this distinction, dihydropyridine CCB toxicity manifests as arterial vasodilation and non-dihydropyridine CCB toxicity is associated with cardiac manifestations such as bradycardia and negative inotropy.2 It is important to note that in high concentrations (such as in overdoses), CCBs lose specificity for their specific receptors and can show all the manifestations of toxicity such as bradycardia, peripheral vasodilation, and hypotension. Patients can develop both vasoplegic shock from peripheral vasodilation and cardiogenic shock. This is a high acuity low occurrence case with infrequently used but specific treatments, and thus this case provides educational value.
EDUCATIONAL OBJECTIVES
At the end of this oral board session, examinees will: (1) demonstrate ability to evaluate a patient with undifferentiated shock with bradycardia and discuss the differential diagnosis, (2) recognize the signs and symptoms of calcium channel blocker overdose, (3) demonstrate ability to manage treatment of a patient with calcium channel overdose.
EDUCATIONAL METHODS
This oral board case followed the standard American Board of Emergency Medicine-style case in a tertiary care hospital with access to all specialists and resources needed. This case was tested using 12 resident volunteers ranging from PGY 1-2 in an ACGME (Accreditation Council for Graduate Medical Education) accredited emergency medicine residency program.
RESEARCH METHODS
Immediate feedback was solicited both from the learners and from the evaluators following the debriefing session. Residents were asked to evaluate the educational value of the case using a 1-5 Likert scale (5 being excellent). Evaluators were asked to score the residents using the ACGME core competencies with a scale of 1-8, 1-4 being unacceptable and 5-8 being acceptable.
RESULTS
Seven PGY1 residents and five PGY2 residents, thus twelve residents in total, completed the case. The average score was 5.10/8. Three residents missed zero critical actions. The most common critical action missed was consulting cardiology or cardiothoracic surgery for circulatory support options. Many residents failed to recognize that the patient did not have a perfusing blood pressure at the beginning of the case and did not start CPR. Although most residents recognized the patient's hemodynamic collapse was from a calcium channel blocker overdose, most did not know the treatment for this beyond atropine and intravenous fluids.The learners rated the educational value of the case as 4.9/5. Seven residents reported that the case definitely increased their medical knowledge; five residents reported that it somewhat increased their medical knowledge. All residents rated the case as helpful in preparing to manage this medical condition.
DISCUSSION
The educational content from this case was effective. This is a high acuity low occurrence case that has unique treatments that are not commonly used. This makes this case excellent for practice and discussion. We learned during implementation that this case has a high degree of difficulty compared to other cases, and junior learners will need more prompting. It is also important for the proctor to keep the case moving because there is a lot to cover in the allotted amount of time.
TOPICS
Calcium channel blocker overdose, toxicology.
PubMed: 38344049
DOI: 10.21980/J8CQ07