Statin Therapy and Pancreatitis: A Multi-Institutional Retrospective Analysis.

INTRODUCTION:  Acute pancreatitis is a serious condition that has numerous etiologies and often requires hospital admission due to its high mortality rates. Statins are used worldwide to reduce the risk of cardiovascular disease. Some studies have shown an association between long-term statin use and acute pancreatitis. However, other studies have shown no effect or even postulated a mild protective effect. Due to conflicting information in the medical literature, the relationship between statins and acute pancreatitis remains unclear. The current study uses the TriNetX global research database to further investigate the impact of statin use on the development of acute pancreatitis over a five-year period. METHODS:  Two cohorts were created using the TriNetX global research database. One group consisted of patients not taking statins, while the other group included patients taking any statins. Patients in both groups were required to be between the ages of 40 and 75 and had normal low-density lipoprotein cholesterol (LDL) (≤200 mg/dl) and triglyceride (≤150 mg/dl) levels. Patients were matched for age, gender, race, and comorbidities. The statin group was then compared to the no-statin group and measured for the outcome of the incidence of acute pancreatitis and the frequency of episodes within the first five years of statin use. Patients who experienced any acute pancreatitis episode before starting statin therapy or before meeting inclusion criteria were excluded from the study. RESULTS:  Patients on statin therapy were significantly more likely to develop acute pancreatitis compared to patients not taking statin therapy (risk ratio 1.332, 95% CI: 1.242-1.429, P<0.0001). However, the statin group had a lower mean number of pancreatitis episodes than the no-statin group (4.6 vs. 5.3, P=0.043). CONCLUSION:  The results from this large global dataset support the previously established idea that prolonged use of statins is associated with an increased risk of pancreatitis. Clinicians should strongly consider statin-induced pancreatitis when other common etiologies have been ruled out.

Efficacy and risk of osteonecrosis of the jaw for pamidronate, zoledronic acid, and denosumab in comparison to alendronate in multiple myeloma patients.

Background: Approximately 70% of multiple myeloma patients develop pathologic fractures. Osteoclast inhibitors can provide reduction in vertebral fractures with an increased risk of osteonecrosis of the jaw (ONJ). ONJ associated with currently used osteoclast inhibitors causes significant morbidity, often from delayed diagnosis and ineffective treatment. Methods: The TriNetX Diamond Network was used to create patient cohorts for each medication: alendronate, pamidronate, zoledronic acid, and denosumab. All patients had a diagnosis of multiple myeloma as identified by International Classification of Disease-10 (ICD-10) code C90.0. Pamidronate, zoledronic acid, and denosumab were each compared to alendronate for 5-year incidence of pathologic vertebral fracture (ICD-10 M48.50XA) and development of ONJ. Results: The 5-year risk of pathologic vertebral fracture was not statistically different between alendronate versus pamidronate, zoledronic acid, and denosumab. However, the 5-year risk of ONJ was significantly higher for both zoledronic acid and denosumab (relative risk 4.85 and 2.9, respectively). Conclusion: This study shows that fracture reduction risk is comparable for all four treatments in multiple myeloma patients, but ONJ risk is lowest for alendronate and pamidronate. Overall, these data support the continued use of pamidronate and alendronate in multiple myeloma patients.

Endoscopic Disease Activity and Biologic Therapy Are Independent Predictors of Suboptimal Bowel Preparation in Patients with Inflammatory Bowel Disease Undergoing Colonoscopy.

BACKGROUND AND AIMS: Optimal bowel preparation (BP) is critical for endoscopic assessment of inflammation and dysplasia in patients with inflammatory bowel disease (IBD). Comorbidities and patient-related factors have been associated with suboptimal BP (SOBP) in the general population. We sought to identify disease-specific characteristics that may impact the quality of BP in patients with IBD. METHODS: We conducted a retrospective analysis of adult IBD patients who underwent outpatient colonoscopies between January 2014 and September 2020 at a large academic medical center. Quality of BP was documented using the Boston Bowel Preparation Scale (BBPS) or the Aronchick scale and dichotomized into "suboptimal" (BBPS 0-5 or Aronchick "fair," "poor," unsatisfactory") and "optimal" (BBPS 6-9 or Aronchick "excellent," "good"). IBD-specific and other factors associated with SOBP were evaluated using logistic regression analyses. RESULTS: Among a total of 395 IBD patients [54% males, mean age 40 years, 63% with Crohn's disease (CD), 35% with ulcerative colitis (UC)], 24.8% had SOBP. On multivariable analysis, moderate-to-severe endoscopic disease vs mild or inactive disease was associated with a higher odds of SOBP [adjusted OR 2.7(95% CI 1.52-4.94)], whereas baseline biologic use was associated with a lower odds of SOBP [aOR 0.24(0.09-0.65)] among the overall IBD cohort. Additionally, age > 65 years [aOR 2.99(1.19-7.54)] and single-dose vs split-dose BP [aOR 2.37(1.43-3.95)] were predictors of SOBP. In the subgroup analysis by IBD type, moderate-to-severe endoscopic disease predicted SOBP among both CD and UC cohorts. CONCLUSION: Endoscopic disease activity was predictive of SOBP, and biologic therapy was protective against SOBP among IBD patients.

The Use of Neodymium-Doped Yttrium Aluminum Garnet Laser for Treatment of Hypertrophic Port-Wine Stain.

Port-wine stains (also called nevus flammeus) are congenital malformations of the capillaries and postcapillary venules. They occur in 0.1-2% of newborns without sex predilection. Although PWS lesions are flat early in life, with age, they become hypertrophic and darker. Pulsed dye laser therapy is the standard of care for treating these lesions, although other laser wavelengths have been utilized with varying degrees of success. We present the case of a gentleman with a hypertrophic PWS who had an excellent response to Nd:YAG laser treatment. The increased tissue penetration of longer laser wavelengths may be of benefit to patients with hypertrophic PWS, and further research into this concept is warranted.

Analysis of Fracture Incidence in 135 Patients With Pregnancy and Lactation Osteoporosis (PLO).

Pregnancy and lactation-related osteoporosis (PLO) is the development of osteoporosis in a premenopausal woman, usually in the third trimester of pregnancy or puerperium. The hormonal changes that allow for the maternal-fetal calcium gradient may be the underlying cause for bone loss, but it is not currently known why some women are affected so severely. Because osteoporosis does not cause symptoms until the condition is advanced, diagnosis is usually made upon the development of an osteoporotic fracture or incidentally when imaging is performed for other reasons. Spontaneous recovery is common once lactation is discontinued, as the underlying hormonal factors that caused the osteoporosis revert to the pre-pregnancy state. We used the research database TriNetX (TriNetX, LLC, Cambridge, MA) to perform a query selecting women between the ages of 10 and 50 years old who experienced an osteoporotic fracture within 12 months of pregnancy. We analyzed the cohort of patients to determine the incidence of fractures at different skeletal locations and evaluated the medications that were utilized in the patients who received treatment.

Increased Risk of Second Primary Malignancy and Mortality at ten Years After Stem Cell Transplant for Multiple Myeloma: An Analysis of 14,532 Patients.

Background The landscape for patients with multiple myeloma has improved dramatically over the last 15 years. Immunomodulatory imide drugs (IMiDs) have shown great efficacy in both the setting of initial therapy and as maintenance after autologous stem cell transplant (ASCT). Concern has arisen, however, regarding the risk of second primary malignancies (SPMs) that appear to be associated with the use of IMiD agents. SPMs are a known sequela of multiple myeloma treatment, particularly as a consequence of maintenance lenalidomide status-post stem cell transplant (SCT). The benefit of SCT has become less clear with the utilization of newer, more effective initial therapies. Objectives To determine the effect of SCT on SPM risk and overall survival in multiple myeloma patients at 5 and 10 years after treatment initiation. Methods We used TriNetX, a global federated health research network providing access to electronic medical records (diagnoses, procedures, medications, laboratory values, genomic information) from approximately 58 million patients in 49 large healthcare organizations. We created two patient cohorts who had all received treatment with thalidomide, lenalidomide, or pomalidomide. One cohort had received SCT while the other had not. Both cohorts were then analyzed for the development of all non-myeloma malignancies which occurred at least one year after initiation of treatment. Results At 5 years, SPMs were 5.8% more likely in patients who received stem cell transplant (22.4% vs 16.6%, RR 0.741, p value <0.0001) but 5-year survival favored transplanted patients by 2.38% (64.85% vs 62.474%, p value 0.0044). 10-year survival favored patients who did not receive transplant by 1.44% (42.279% vs 40.838%, p value 0.0279). The Kaplan-Meier curves cross at year 6. Conclusions It has previously been shown that the use of alkylating agents in myeloma patients significantly increases the risk of SPM, but that difference had curiously not been shown to have a negative impact on survival. Our analysis shows that this negative survival impact does exist but requires six or more years of follow up to become evident. Recent analyses from studies using older regimens show no overall survival benefit from the use of stem cell transplant. As non-transplant regimens become more effective at producing minimal residual disease (MRD) negativity, it seems that transplantation for myeloma patients will soon be regarded as unnecessary or even detrimental.

Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors and Lung Cancer: History, Epidemiology, and Market Outlook.

Lung cancer is a leading cause of death for both men and women. The treatment of lung cancer has been stifled with pessimism for many years. However, molecularly targeted therapies directed at pathologic epidermal growth factor receptor tyrosine kinases have come to market and, with them, a new tone to an old diagnosis. Treatment of lung cancer is a complex science that requires not only anatomical knowledge of the patient but also an understanding of the patient's overall physiologic condition. When patients are treated appropriately, this drug can transform the natural progression of their disease and improve survival. Interestingly, the clinical solidarity of these first-generation tyrosine kinase inhibitors (TKIs) has become the prelude to a second wave of advances in molecular targeting that we can expect to further improve how we classify and treat lung cancers. Cancers that become resistant to epidermal growth factor receptor (EGFR)-specific TKIs through a secondary mutation are likely to be dependent on the activated kinase for their growth and survival. Therefore, discovering a secondary means of inhibiting EGFR T790M may be therapeutically necessary. This has prompted the preclinical and clinical development of second and third-generation kinase inhibitors. Tumor subtypes are also now being identified, potentially allowing patients to be treated with drugs that most benefit their tumor subtype. We used the TriNetX research platform to analyze the rate of patients being prescribed first, second, and third-generation EGFR TKIs and propose a rationale for the trends seen over time.

Corticosteroid and Biologic Use Not Associated With Adverse Outcomes for Inflammatory Bowel Disease Patients Hospitalized With COVID-19.

BACKGROUND: To date, studies investigating the inflammatory bowel disease (IBD) patient experience with coronavirus disease 2019 (COVID-19) have consistently reported that the observed rate of COVID-19 within this population is similar to the general population. Limited research has suggested that corticosteroid use in the IBD population may be associated with worse COVID-19 outcomes, but it is still yet to be determined if specific IBD-related clinical factors are associated with worse outcomes. Our goal was to describe clinical COVID-19 outcomes for IBD patients and to identify the clinical factors that may be associated with worse outcomes. METHODS: In this retrospective study, we utilized the inpatient database within the largest hospital network in the New York City Metropolitan area to identify all IBD patients with confirmed COVID-19. RESULTS: Of 83 IBD/COVID-19 patients presenting to a hospital network emergency room, 56 were hospitalized. Overall, 19.6% of hospitalized IBD patients died, compared with 22.2% of all hospital system COVID-19 patients during the time period. There was no association between pre-admission corticosteroid use or biologic treatment with a severe course of COVID-19. CONCLUSIONS: In contrast to some prior reports, we did not observe an association of pre-admission corticosteroid use and adverse outcomes. While the mortality rate was high for IBD/COVID-19 patients, it was not greater than that for hospitalized COVID-19 patients generally. Though our results are encouraging, we continue to support the recommendations of the leading gastrointestinal and IBD societies to regard our patients as "at risk", and to observe caution in their care.

Usefulness of nivolumab plus ipilimumab immunotherapy for metastatic uveal melanoma.

A 53-year-old woman with known localized uveal melanoma presented with pain from a large destructive lesion of the left iliac bone. Biopsy confirmed metastatic melanoma, and positron emission tomography scan showed extensive osseous destruction. Because her uveal melanoma was successfully treated with brachytherapy 15 years earlier, next-generation sequencing was performed, and a GNAQ mutation proved the lesion to be of uveal origin. Uveal melanoma has a worse prognosis than cutaneous melanoma. We initiated treatment with the combination of nivolumab and ipilimumab, and after four cycles of treatment a positron emission tomography scan showed resolution of all prior lesions. The patient was then placed on maintenance therapy.

Validation of a wearable biosensor device for vital sign monitoring in septic emergency department patients in Rwanda.

OBJECTIVE: Critical care capabilities needed for the management of septic patients, such as continuous vital sign monitoring, are largely unavailable in most emergency departments (EDs) in low- and middle-income country (LMIC) settings. This study aimed to assess the feasibility and accuracy of using a wireless wearable biosensor device for continuous vital sign monitoring in ED patients with suspected sepsis in an LMIC setting. METHODS: This was a prospective observational study of pediatric (≥2 mon) and adult patients with suspected sepsis at the Kigali University Teaching Hospital ED. Heart rate, respiratory rate and temperature measurements were continuously recorded using a wearable biosensor device for the duration of the patients' ED course and compared to intermittent manually collected vital signs. RESULTS: A total of 42 patients had sufficient data for analysis. Mean duration of monitoring was 32.8 h per patient. Biosensor measurements were strongly correlated with manual measurements for heart rate (r = 0.87, p < 0.001) and respiratory rate (r = 0.75, p < 0.001), although were less strong for temperature (r = 0.61, p < 0.001). Mean (SD) differences between biosensor and manual measurements were 1.2 (11.4) beats/min, 2.5 (5.5) breaths/min and 1.4 (1.0)°C. Technical or practical feasibility issues occurred in 12 patients (28.6%) although were minor and included biosensor detachment, connectivity problems, removal for a radiologic study or exam, and patient/parent desire to remove the device. CONCLUSIONS: Wearable biosensor devices can be feasibly implemented and provide accurate continuous heart rate and respiratory rate monitoring in acutely ill pediatric and adult ED patients with sepsis in an LMIC setting.