The impact of the California state lockdown during the COVID-19 pandemic on management of patients with pancreatic ductal adenocarcinoma.

BACKGROUND AND OBJECTIVES: The SARS-COVID-19 pandemic significantly limited healthcare access. We sought to evaluate whether California's lockdown in March 2020 affected staging and time to treatment of pancreatic ductal adenocarcinoma (PDAC). We hypothesized that patients diagnosed after the lockdown would have longer time to treatment and higher stage at presentation. METHODS: We retrospectively identified and categorized 1294 patients presenting to five University of California healthcare systems with a new diagnosis of PDAC into "pre-lockdown" and "post-lockdown" groups based on timing of pathologic diagnosis. RESULTS: In the 12 months pre-lockdown, 835 patients were diagnosed with PDAC, and 459 patients in the 6 months post-lockdown. Demographics, staging, and treatment type were similar between eras. There was a decreased male:female ratio post- versus pre-lockdown (0.97 vs. 1.25; p = 0.03). Time from symptom onset to first treatment was significantly increased among females post-lockdown (p = 0.001). However, overall time from diagnosis to first treatment was shorter in the post-lockdown era (median 23 vs. 26 days, p < 0.001). CONCLUSIONS: The COVID-19 lockdown did not significantly delay initial presentation, diagnosis, or treatment of newly diagnosed PDAC patients. Time from diagnosis to first treatment was shorter post-lockdown. Reduced healthcare utilization for minor complaints and increased telehealth utilization may have contributed.

Hereditary Cancer Clinics Improve Adherence to NCCN Germline Testing Guidelines for Pancreatic Cancer.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis, with a 5-year overall survival rate of 10%. In November 2018, NCCN recommended that all patients with PDAC receive genetic counseling (GC) and germline testing regardless of family history. We hypothesized that patients with PDAC were more likely to be referred for testing after this change to the guidelines, regardless of presumed predictive factors, and that compliance would be further improved following the implementation of a hereditary cancer clinic (HCC). METHODS: We conducted a single-institution retrospective analysis of patients diagnosed with PDAC from June 2017 through December 2021 at University of California, Irvine. We compared rates of genetics referral among patients in different diagnostic eras: the 18-month period before the NCCN Guideline change (pre-NCCN era: June 2017 through November 2018), 14 months following the change (post-NCCN era: December 2018 through January 2020), and 18 months after the creation of an HCC (HCC era: June 2020 through December 2021). Family and personal cancer history, genetics referral patterns, and results of GC were recorded. Data were compared using chi-square, Fisher exact, and multivariate analyses. RESULTS: A total of 335 patients were treated for PDAC (123 pre-NCCN, 109 post-NCCN, and 103 HCC) at University of California, Irvine. Demographics across groups were comparable. Prior to the guideline changes, 30% were referred to GC compared with 54.7% in the post-NCCN era. After the implementation of the HCC, 77.4% were referred to GC (P<.0001). The odds ratio (OR) for referral to GC among patients with a positive family history of cancer progressively decreased following the change (pre-NCCN era: OR, 11.90 [95% CI, 3.00-80.14]; post-NCCN era: OR, 3.39 [95% CI, 1.13-10.76]; HCC era: OR, 3.11 [95% CI, 0.95-10.16]). CONCLUSIONS: The 2018 updates to the NCCN Guidelines for PDAC recommending germline testing for all patients with PDAC significantly increased GC referral rates at our academic medical center. Implementation of an HCC further boosted compliance with guidelines.

Heterozygous Alpha-1 Antitrypsin Deficiency Causing Pulmonary Emboli and Pulmonary Bullae.

Alpha-1 antitrypsin deficiency is an autosomal co-dominant disease known for different genetic alterations in the serine protease inhibitor enzyme by which different disease phenotypes can manifest. The lung and the liver are the most common organs involved. The severity of the disease depends on the phenotypes involved. However, emerging evidence shows that this disease can impact multiple organ systems and may even develop regardless of the phenotype. We describe a case of a young man with a known history of the MS phenotype who presented with chest pain and was found to have pulmonary emboli and bullae. His past medical history was relevant for a gastric ulcer and elevated liver enzymes. Due to this young man's age and lack of risk factors for the aforementioned diseases, we propose that these findings were manifestations of his MS phenotype. This case raises multiple questions challenging the presumed benign nature of the MS phenotype. We propose a closer follow-up and lower threshold for diagnostic studies in patients with the heterozygous form.

A 64-year-old woman with rapid neurologic decline diagnosed with Toxoplasma encephalitis after presumed metastatic cancer.

In an era of fragmented medical care, concurrent clinical features that ultimately lead to a unified diagnosis may not be prioritized appropriately. We present a case of a 64-year-old woman referred to hematology clinic for anemia, with recent memory loss and gait disturbance. Two months later, she developed pneumonia; imaging workup showed a left renal mass. Neurologic function continued to decline precluding definitive nephrectomy. She then presented with new-onset seizure and initial neuro-imaging was reported as unremarkable. One month later, outpatient neurologic workup demonstrated new left-sided weakness which prompted hospitalization and repeat neuro-imaging, which showed a 1.7-cm right frontal lobe mass lesion with surrounding vasogenic edema. The patient ultimately underwent craniotomy with resection of the mass lesion; pathology did not show metastatic renal cell cancer, the provisional clinical diagnosis. Rather, immunostaining revealed a parasite and ultimately led to a diagnosis of Toxoplasma encephalitis, an infection whose clinical presentation had been interpreted by healthcare providers for months to be a result of metastatic cancer.

Primary Refractory Catastrophic Antiphospholipid Syndrome Masquerading as Buerger's Disease.

Catastrophic antiphospholipid syndrome (CAPS) is a lethal disease with up to 30% mortality rate. It can occur as a primary disease or secondary to an underlying autoimmune disease. Current treatment focuses on disease control with anticoagulation and steroids. Plasma exchange and intravenous immunoglobulin (IVIG) have shown some benefit when added. Monoclonal drugs such as rituximab have shown some benefit in refractory cases, and eculizumab, a drug approved for use in atypical hemolytic uremic syndrome, has demonstrated disease control in a few case reports. We describe a unique case of primary refractory CAPS with an unusual presentation that was treated with five lines of therapy before disease control was established.

Do Nonsteroidal Anti-Inflammatory Drugs Have a Deleterious Effect on Cartilage Repair? A Systematic Review.

OBJECTIVES: The purpose of this study was to systematically review the available evidence regarding any plausible deleterious effects of nonsteroidal anti-inflammatory drugs (NSAIDs) on chondrocytes, chondrocyte differentiation, and allograft or autograft incorporation after cartilage repair procedures. DESIGN: Three databases (PubMed, Science Direct, and Cochrane Library) were screened for eligible studies: investigating the effects of NSAIDs on chondrocytes, chondrogenic differentiation, or allograft/autograft incorporation. This evaluation included studies of any level of evidence, written in English, reporting clinical or preclinical results, published in peer review journals and dealing with our topic. All articles evaluating the effects of NSAIDs on either osteoarthritic (OA) chondrocyte samples or OA chondrocyte models were excluded. Moreover, articles about bone healing in which allograft or autograft incorporation was not investigated were also excluded. Methodologic quality assessment was performed for in vivo animal studies according to ARRIVE guidelines, and risk of bias of each included study was identified using the ROBINS-I tool. RESULTS: Eighteen studies were included in the review: 4 in vitro studies, 13 animal studies, and 1 human study. According to these studies NSAIDs have no detrimental effect on healthy mature chondrocytes; however, these drugs influence chondrocyte differentiation and graft incorporation and therefore may interfere with chondrogenesis and incorporation after transplantation of chondrocytes or osteochondral grafts. CONCLUSION: The use of NSAIDs, systemic or local, after cartilage repair procedures should be avoided unless a substantial clinical benefit would otherwise be withheld from the patient. More human studies are needed to analyze the effect of NSAIDs on cartilage repair.

Simultaneous Determination of Everolimus, Sirolimus, Tacrolimus, and Cyclosporine-A by Mass Spectrometry.

Measurement of immunosuppressive drug concentrations cyclosporine A (CyA), tacrolimus (TAC), sirolimus (SIR), and everolimus (EVE) in blood is an important application of therapeutic drug monitoring. These immunosuppressive agents are used in combined regimens and nowadays the liquid chromatography and tandem mass spectrometry is the best option for simultaneous analysis of these drugs in one short run. We developed an liquid chromatography and tandem mass spectrometry methodology in-house to measure the combination of immunosuppressants in a single blood sample from transplant patients in Brazil. We analyzed 235 combinations of 4 immunosuppressive drugs in patient blood to validate this study. The measuring ranges were 9 to 1000 ng/mL for CyA and 2 to 50 ng/mL for TAC, SIR, and EVE. Accuracy of the method was between 83.87% and 126.6% (coefficient of determination [r2] > 0.995). Validation of variation was ≤15% for lower limit of quantification. In our analysis 20% of patients treated with EVE showed concentration range of 6 to 6.9 ng/mL, 28% of patients treated with SIR showed a concentration range of 4 to 4.9 ng/mL to TAC, 22% of patients showed concentration range of 5 to 5.9 ng/mL, and finally 50% of patients treated with CyA showed concentration range of 20 to 30 ng/mL. Our routine laboratory was able to implement this new methodology in-house to measure simultaneous CyA, TAC, SIR, and EVE in a single blood sample from transplant patients with a sensibility and rapid quantification analysis.

Ureterocalicostomy with lower pole nephrectomy in a renal transplant: A case report.

As the number of kidney transplants continues to rise, so does the number and complexities of surgical-related complications, which may be associated with increased morbidity and potentially graft loss. Ureteral stenosis, the most prevalent urological complication, may require diverse techniques for surgical correction depending on several recipient and graft abnormalities. Here we report the surgical and clinical outcomes of a 62-year-old man with a posttransplant pyeloureterostomy stricture successfully treated with ureterocalicostomy after a lower pole nephrectomy. Although the resection of renal parenchyma may prevent a stenosis recurrence, surgeons can be reluctant to use this strategy due to the possible negative impact on renal function. We highlight some key steps of the surgical technique to prevent unnecessary allograft lesion and present short-term outcomes, suggesting that this rarely described procedure is a safe and effective alternative treatment for kidney transplant recipients with pyeloureterostomy stenosis.