Double Trouble Research Articles

Double trouble: A case of synchronous presentation of acute myeloid leukaemia and multiple myeloma

Malignancies following successful chemotherapy for various malignant diseases, including multiple myeloma (MM), are well known and documented. The occurrence of acute myeloid leukaemia (AML) after chemotherapy for MM with alkylating agents is well described; however, simultaneous occurrence of the two entities with no prior therapy is extremely rare. We describe a case of an elderly patient with no previous exposure to chemotherapy, who was diagnosed with both MM and AML concurrently. Very few similar cases have been described in the literature.

Double trouble - thyro-pericarditis: rare presentation of Graves' disease as pericarditis-a case report.

BackgroundAcute pericarditis is frequently encountered in clinical practice; however, pericarditis as the first presentation of Graves' disease is rare and mainly limited to case reports in the literature. We hereby report a case in which a young patient presented with pericarditis as the first manifestation of Graves’ disease.Case summaryA 24-year-old male was admitted to hospital with presenting complaint of left-sided chest pain, gradual in onset, 6/10 in intensity, sharp in character, increased by deep breathing and improved by leaning forward. Patient also gave a history of insomnia, unintentional weight loss despite a good appetite, heat intolerance, and anxiety. On clinical examination, the patient had features of thyrotoxicosis, i.e., tachycardia, high volume pulse, and sweaty palms with fine tremors. There was no associated pericardial rub. Neck examination shows diffuse, non-tender goitre. Electrocardiogram findings were consistent with acute pericarditis. His thyroid function tests demonstrated hyperthyroidism and anti-thyroglobulin antibodies were also significantly elevated. Echocardiogram showed preserved left ventricular systolic function and a small global pericardial effusion without any signs of tamponade. He was diagnosed with Graves’ disease revealing itself as pericarditis and was started on ibuprofen, beta-blockers, and carbimazole. Patient had marked clinical and biochemical improvement on 3 monthly follow-ups.DiscussionThyro-pericarditis is a rare entity, and limited literature is available regarding this combination. The exact aetiology of Graves associated pericarditis is unknown. There is a possibility of interaction of autoantibodies with receptors on pericardium. Diagnosis is based on a detailed history, clinical examination, supplemented by relevant investigations (elevated free T4 and thyroid receptor antibodies, suppressed thyroid stimulating hormone (TSH) and Imaging via ultrasound). Mainstay of treatment includes non-steroidal anti-inflammatory drugs, beta-blockers, and anti-thyroidal medications.

Double trouble: combined cardiovascular effects of particulate matter exposure and coronavirus disease 2019.

The coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly grown into a pandemic. According to initial reports, the lungs were thought to be the primary target, but recent case studies have shown its reach can extend to other organs including the heart and blood vessels. The severity of cardiac complications of COVID-19 depends on multiple underlying factors, with air pollutant exposure being one of them, as reported by several recent studies. Airborne particulate matter (PM) attracts heightened attention due to its implication in various diseases, especially respiratory and cardiovascular diseases. Inhaled PM not only carries microorganisms inside the body but also elicits local and systemic inflammatory responses resulting in altering the host’s immunity and increasing susceptibility to infection. Previous and recent studies have documented that PM acts as a ‘carrier’ for the virus and aids in spreading viral infections. This review presents the mechanisms and effects of viral entry and how pollution can potentially modulate pathophysiological processes in the heart. We aimed to concisely summarize studies examining cardiovascular outcomes in COVID-19 patients and postulate on how PM can influence these outcomes. We have also reviewed evidence on the use of renin–angiotensin system inhibitors, namely angiotensin-converting enzyme inhibitors and angiotensin receptor blockers, in patients with COVID-19. The interplay of pollution and SARS-CoV-2 is essential to understanding the effects of accentuated cardiovascular effects of COVID-19 and deserves in-depth experimental investigations.

Double trouble? Impact of frozen embryo transfer on the monozygotic twinning rate: a retrospective cohort study from 8459 cycles.

To compare monozygotic twinning (MZT) rates in patients undergoing fresh embryo transfer (ET) and frozen embryo transfer. All clinical pregnancies after single ET carried out in our IVF center between 2014 and 2018 (n = 8459) were retrospectively analyzed for the incidence of MZT. MZT rate was compared in women who underwent fresh ET (n = 3876) and frozen ET (n = 4583). There was a total of 120 MZT identified in the fresh ET group (3.10%) and 103 MZT in the frozen ET group (2.25%), which was significant (p = 0.015). In the univariate analysis, the risk of MZT was decreased with frozen embryo transfer (OR 0.72; 95% CI, 0.55-0.94, p = 0.016) and increased with mild stimulation protocol in the fresh cycle (OR 1.90; 95% CI, 1.04-3.45, p = 0.036). Multivariable logistic regression revealed that frozen embryo transfer was associated with a significant decrease risk of MZT (adjusted OR 0.66; 95% CI, 0.46-0.90, p = 0.011). Frozen ET is associated with a lower risk of MZT.

Double trouble: the implications of climate change for biological invasions

The implications of climate change for biological invasions are multifaceted and vary along the invasion process. Changes in vectors and pathways are likely to manifest in changes in transport routes and destinations, together with altered transit times and traffic volume. Ultimately, changes in the nature of why, how, and where biota are transported and introduced will pose biosecurity challenges. These challenges will require increased human and institutional capacity, as well as proactive responses such as improved early detection, adaptation of present protocols and innovative legal instruments. Invasion success and spread are expected to be moderated by the physiological response of alien and native biota to environmental changes and the ensuing changes in biotic interactions. These in turn will likely affect management actions aimed at eradicating, containing, and mitigating invasions, necessitating an adaptive approach to management that is sensitive to potentially unanticipated outcomes.

Double Trouble: Impact of Hearing, Vision Loss on Dementia Risk

Double Trouble: Impact of Hearing, Vision Loss on Dementia Risk

Double Trouble with Pembrolizumab: Immune Checkpoint Inhibitor-Induced Type 1 Renal Tubular Acidosis and Secondary Adrenal Insufficiency

Double Trouble with Pembrolizumab: Immune Checkpoint Inhibitor-Induced Type 1 Renal Tubular Acidosis and Secondary Adrenal Insufficiency

Double trouble? The communication dimension of the reproducibility crisis in experimental psychology and neuroscience

Most discussions of the reproducibility crisis focus on its epistemic aspect: the fact that the scientific community fails to follow some norms of scientific investigation, which leads to high rates of irreproducibility via a high rate of false positive findings. The purpose of this paper is to argue that there is a heretofore underappreciated and understudied dimension to the reproducibility crisis in experimental psychology and neuroscience that may prove to be at least as important as the epistemic dimension. This is the communication dimension. The link between communication and reproducibility is immediate: independent investigators would not be able to recreate an experiment whose design or implementation were inadequately described. I exploit evidence of a replicability and reproducibility crisis in computational science, as well as research into quality of reporting to support the claim that a widespread failure to adhere to reporting standards, especially the norm of descriptive completeness, is an important contributing factor in the current reproducibility crisis in experimental psychology and neuroscience.

The sequel to COVID-19: the antithesis to life

The sequel to COVID-19: the antithesis to life

S1426 Double Trouble: Chronic Pancreatitis and an Overlooked Superior Mesenteric Vein Thrombosis

INTRODUCTION: Chronic pancreatitis is a challenging disease process to manage. Abdominal pain is the most common, debilitating symptom for these patients. Here, we outline the outpatient approach and management of a patient with chronic pancreatitis who also had concomitant mesenteric venous thrombosis. CASE DESCRIPTION\METHODS: A 56-year-old man with history of tonsillar squamous cell carcinoma and non-small cell lung cancer treated with radiation, coronary artery disease, heavy tobacco use, cholecystectomy, and chronic pancreatitis complicated by pseudocysts and exocrine insufficiency presented to internal medicine clinic with persistent epigastric pain. Three years ago, he was diagnosed with chronic pancreatitis, secondary to heavy alcohol and tobacco use. In the interim, he quit alcohol, reduced smoking, and went through multiple therapeutic regimens including gabapentin, opioids, pancreatic enzyme replacement, and celiac plexus block. On exam, he was hemodynamically stable but in discomfort due to pain. He was cachectic and had epigastric tenderness without rebound tenderness or guarding. Laboratory tests revealed cholestatic transaminitis. We referred him to a gastroenterologist. MRCP showed irregular contour of the pancreas with smooth narrowing in the pancreatic neck concerning for a stricture. EGD and EUS were planned. Duloxetine was added to his regimen. However, MRI revealed an occlusion of the superior mesenteric vein at the level of the portal confluence with multiple collateral vessels at the root of the mesentery. Prior CT scan showed the presence of thrombus two years ago. Medical record did not reveal any management of the thrombus and the patient was unaware of the condition. He did not have evidence of portal hypertension. Given the severity of the symptoms and lack of prior anticoagulation, we started him on rivaroxaban. Despite this intervention, he continued to have flares of chronic pancreatitis in the subsequent months and will undergo another celiac plexus block. DISCUSSION: Chronic mesenteric venous thrombosis is often an incidental finding on imaging and usually asymptomatic. This is mainly considered a consequence of venous stasis and endothelial injury, compounded by risk factors such as local inflammation (e.g., pancreatitis), abdominal tumors or pseudocysts, and acquired thrombophilia. Anticoagulation is generally recommended. In the absence of predisposing illness or a hypercoagulable state, further work-up for portal hypertension and referral to hematology are indicated.

Effective Therapy or Double Trouble? Simultaneous ECMO and Thrombolysis of Acute Massive Pulmonary Embolism

Effective Therapy or Double Trouble? Simultaneous ECMO and Thrombolysis of Acute Massive Pulmonary Embolism

Rigorous Computational Study Reveals What Docking Overlooks: Double Trouble from Membrane Association in Protein Kinase C Modulators

Increasing protein kinase C (PKC) activity is of potential therapeutic value. Its activation involves an interaction between the C1 domain and diacylglycerol (DAG) at intracellular membrane surfaces; DAG mimetics hold promise as new drugs. We previously developed the isophthalate derivative HMI-1a3, an effective but highly lipophilic (clogP = 6.46) DAG mimetic. Although a less lipophilic pyrimidine analog, PYR-1gP (clogP = 3.30), gave positive results in computational docking, it unexpectedly presented greatly diminished binding to PKC in vitro. Through more rigorous computational molecular modeling, we reveal that, unlike HMI-1a3, PYR-1gP forms an intramolecular hydrogen bond, which both obstructs binding and reorients PYR-1gP in the membrane in a fashion that prevents it from correctly accessing the PKC C1 domain. Our results highlight the great value of molecular dynamics simulations as a key component for the drug design process of ligands targeting weakly membrane-associated proteins, where simulation in the relevant membrane environment is crucial for obtaining biologically applicable results.

Double Trouble: Complications in Twin Pregnancies.

With the increasing rate of twin pregnancies due to increase in maternal age and use of assisted reproduction, it is important to be aware of unique diseases which occur specifically to twin pregnancies, especially in monochorionic twin pregnancies. These entities include twin to twin transfusion syndrome, twin anemia polycythemia sequence, twin reversed arterial perfusion, cotwin demise, and conjoined twins. Early evaluation and documentation are imperative to guide management which ultimately leads to better patient outcomes.

COVID-19 pandemic: a double trouble for Indian adolescents and young adults living with type 1 diabetes.

BackgroundStrict isolation measures and interrupted health care services during the COVID 19 pandemic are contemplated to instigate stress universally, particularly in those with chronic illnesses such as type 1 diabetes (T1D).MethodsA cross-sectional, observational study was done to assess determinants of stress and its impact on glycemic control in adolescents and young adults (aged 12–24 years) living with T1D in India. An online, semi-structured survey including Perceived Stress Scale (PSS-10) was distributed and results were analyzed.ResultsA total of 89 participants (46 males, mean age 19.61 ± 3.8 years) with T1D completed the survey. Age (r = 0.325, p = 0.005) and HBA1C level within the preceding 3 months (r = 0.274, p = 0.036) correlated positively with PSS-10 scores. There was a statistically significant difference in PSS-10 score based on gender (t(70) = − 2.147; p = 0.035), education (F (4,67) = 4.34, p = 0.003), and occupation (F(3,68) = 4.50, p = .006). On multiple linear regression, gender, occupation, and HbA1C were the significant determinants of PSS-10 (F(3,55) = 12.01, p < 0.001, R2 = 0.363). One-way ANOVA showed a significant impact of mean PSS-10 score on the glycemic control (F(2,69) = 3.813, p = 0.027).ConclusionAn increased prevalence of stress was seen among Indian adolescents and young adults living with T1D. Female gender, salaried individuals, and pre-existing poorly controlled diabetes contributed to an increased risk of stress. Increased stress resulted in worsened glycemic control.

Pilar Catalán.

Pilar Catalán.

Subtrochanteric fracture in a near term pregnant female in the back drop of COVID-19 pandemic: A triple trouble pregnant with peril all along

Outbreak of severe acute respiratory syndrome corona virus was first reported in Wuhan province in China. By February all hell broke loose in Europe and other continents. Spread of virus in India with 1.38 billion population posed an unprecedented challenge to its health care system. We hereby report a rare case of subtrochanteric fracture of femur in a near term (35 weeks) pregnant female who was treated at our tertiary care center in the times of Covid-19. Combination of pregnancy and Subtrochanteric femoral fracture is a double trouble with high morbidity and mortality and in time of Corona pandemic it became a unique challenge where two lives were at risk. Here we share our experience of dealing this case with multidisciplinary approach and sticking to our clinical sense as literature for Covid-19 pandemic is barely 4 months old and devoid of any guideline for such cases so far.

Double trouble? Clinic-specific risk factors for monozygotic twinning

To investigate clinic-specific risk factors for monozygotic twinning (MZT) using a large, electronic database. Retrospective case-control study. Infertility clinics. Using an electronic medical record system, viable clinical pregnancy (confirmation of a gestational sac(s) and presence of at least one fetal pole with a heartbeat on first trimester ultrasound), data were obtained from homologous invitro fertilization (IVF) cycles after single ET from June 1, 2004, to December 31, 2016. Monozygotic twinning was defined as a pregnancy with two fetal heartbeats on ultrasound with sex concordance at birth. None. Risk factors for MZT including cycle type, method of insemination, and method of cryopreservation. Of the 28,265 IVF cycles that met inclusion criteria over the study period, 8,749 (31.0%) resulted in a viable intrauterine clinical pregnancy. There were 102 (2.7%) MZT in the fresh cycle cohort and 133 (2.7%) in the frozen cycle cohort. Neither cryopreservation nor the method of cryopreservation was a significant risk factor for MZT. However, the use of sequential media was an independent risk factor for MZT in fresh, but not frozen, ETs (odds ratio = 1.72, 95% confidence interval, 1.10-2.68). Significant differences were seen in the incidence of MZT between clinics, and this difference persisted after controlling for known risk factors (clinic 0, reference; clinic 2, odds ratio = 2.22; 95% confidence interval, 1.48-3.32; clinic 3, odds ratio = 1.93; 95% confidence interval, 1.30-2.87). Differences in MZT rates exist between individual IVF clinics, suggesting that variations in practice patterns may contribute to this event. The present study noted the use of sequential media was an independent risk factor for fresh but not frozen cycles.

Posterior Cranial Fossa Maldevelopment in Infants with Repaired Open Myelomeningoceles: Double Trouble or a Dynamic Process of Posterior Cranial Fossa Abnormalities?

Two degrees of posterior cranial fossa (PCF) maldevelopment can be hypothesized in children with myelomeningocele (MMC). This paper investigates the PCF deformation by quantitative magnetic resonance imaging analysis in MMC subjects with and without Chiari 2 malformation (CM2). PCF bone volume (PCFV), PCF brain volume (PCFBV), lengths of PCF, ventriculomegaly, level, and extension of the dysraphism were analyzed by magnetic resonance image scanning of 51 newborns with MMC surgically repaired at birth (and 41 controls). The possible correlation among PCF hypoplasia, level/extension of the spinal dysraphism, and ventriculomegaly was assessed. In MMC and CM2, the dysraphism level was above L4 in 30 and below L4 in 10 subjects. PCFV/PCFBV ratio and supraocciput and exocciput lengths were significantly reduced; foramen magnum diameters, mammillo-pontine distance, and pons length were significantly increased (P< 0.05). In isolated MMC, the dysraphism level was below L4 in all cases. PCFV/PCFBV ratio and supraocciput length were significantly reduced; pons length was significantly increased (P < 0.05). The lower the MMC level, the lower the incidence of CM2. A positive correlation was found between PCF hypoplasia and MMC level above L4 (P < 0.001), while a negative correlation was found among PCF hypoplasia and MMC extension (P= 0.006), PCF hypoplasia, and ventriculomegaly (P= 0.02). PCF hypoplasia has to be considered a dynamic maldevelopment process in the 2 cohorts rather than 2 separated entities. The level of MMC is the main but not the unique cause influencing the severity of PCF maldevelopment.

Hypokalaemic Paralysis - A double trouble from concurrent Thyrotoxicosis and Gitelman syndrome: A report of two cases

Background Hypokalaemic paralysis is a rare group of disorders with concomitant muscle weakness and hypokalaemia. Thyrotoxicosis is a recognized and a common cause for hypokalaemic paralysis among Asians, in which intracellular shift of potassium is enhanced. Gitelman syndrome, an autosomal recessive renal salt loosing condition is characterized by hypokalaemia, hypocalciuria and hypomagnesaemia. Concurrence of these two conditions is very rarely reported. Case Presentation We report two genetically unrelated Sri Lankan patients who presented with concurrent thyrotoxicosis and Gitelman syndrome. Both of them presented with symptomatic hypokalaemia and detected to have thyrotoxicosis. One had Grave’s disease, while the other patient had toxic multinodular goiter. They were initially managed symptomatically for thyrotoxic hypokalaemic paralysis. Despite rendering euthyroidism with medical management, they persisted to have symtomatic hypokalaemia. On evaluation for a second pathology, we detected them to have Gitelman syndrome, which is a rare concurrence. Conclusion Elevated thyroid hormone levels can precipitate a paralytic episode in a patient with subclinical chronic hypokalaemia due to an additional underlying disease. Gitelman syndrome is such a disease which should be considered and actively looked for in a patient with persistent hypokalaemia following rendering euthyroidism.

Double Trouble: Treatment Considerations for Patients with Comorbid PTSD and Depression

Posttraumatic stress disorder (PTSD) rarely occurs alone, with an approximate 80% syndromal comorbidity rate of which 50% is major depression. Evidence-based psychotherapy is the first-line treatment for PTSD and is very efficacious in some, but is directed toward PTSD symptomatology not depression, and many do not fully recover. This review presents the evidence for psychotherapy, pharmacotherapy, neurostimulation, and combinations of these modalities in treating PTSD with comorbid depression. Modifications to evidence-based psychotherapy for PTSD and comorbid depression can be made to involve comorbid traumatic brain injury and early childhood adversity, and although effective, some studies show such adaptations may not be necessary. Burgeoning neuromodulation research holds promise for possible additions to the current first-line treatment and new core treatment options. Cognitive processing therapy and prolonged exposure are the most cited effective treatments for PTSD; arguments for adding an antidepressant in cases of significant comorbid depression are supported by research. Treating PTSD first when comorbid with depression is supported by evidence that trauma-focused therapies reduce depressive symptoms whereas depression-focused treatments do not show the same for comorbid PTSD. Future directions for study will involve new sequencing and combinations of current treatment modalities in addition to exploration of other factors including biomarkers, resiliency, and risk factors to inform novel treatment options for this population.