Substance use and other factors associated with COVID-19 vaccine uptake among people at risk for or living with HIV: Findings from the C3PNO consortium.

Objective: We describe the prevalence of COVID-19 vaccine uptake, substance use, and other factors associated with vaccine hesitancy among participants from nine North American cohort studies following a diverse group of individuals at risk for or living with HIV. Methods: Between May 2021 and January 2022, participants completed a survey related to COVID-19 vaccination. Participants included those with and without substance use. Those responding as 'no' or 'undecided' to the question "Do you plan on getting the COVID-19 vaccine?" were categorized as vaccine hesitant. Differences between groups were evaluated using chi-square methods and multivariable log-binomial models were used to calculate prevalence ratios (PR) of COVID-19 vaccine hesitancy with separate models for each substance. Results: Among 1,696 participants, COVID-19 vaccination was deferred or declined by 16%. Vaccine hesitant participants were younger, with a greater proportion unstably housed (14.8% vs. 10.0%; p = 0.02), and not living with HIV (48.% vs. 36.6%; p <.01). Vaccine hesitant participants were also more likely to report cannabis (50.0% vs. 42.4%; p = 0.03), methamphetamine (14.0% vs. 8.2%; p <.01), or fentanyl use (5.5% vs. 2.8%; p = 0.03). Based on multivariable analyses methamphetamine or fentanyl use remained associated with COVID-19 vaccine hesitancy (Adjusted PR = 1.4; 95% CI 1.1-1.9 and Adjusted PR = 1.6; 95% CI 1.0-2.6, respectively). Conclusion: As new COVID-19 vaccines and booster schedules become necessary, people who use drugs (PWUD) may remain vaccine hesitant. Strategies to engage hesitant populations such as PWUD will need to be tailored to include special types of outreach such as integration with substance use programs such as safe injection sites or recovery programs.

Competent immune responses to SARS-CoV-2 variants in older adults following two doses of mRNA vaccination.

Aging is associated with a reduced magnitude of primary immune responses to vaccination. mRNA-based SARS-CoV-2 vaccines have shown efficacy in older adults but virus variant escape is still unclear. Here we analyze humoral and cellular immunity against an early-pandemic viral isolate and compare that to the P.1 (Gamma) and B.1.617.2 (Delta) variants in two cohorts (<50 and >55 age) of mRNA vaccine recipients. We further measure neutralizing antibody titers for B.1.617.1 (Kappa) and B.1.595, with the latter SARS-CoV-2 isolate bearing the spike mutation E484Q. Robust humoral immunity is measured following second vaccination, and older vaccinees manifest cellular immunity comparable to the adult group against early-pandemic SARS-CoV-2 and more recent variants. More specifically, the older cohort has lower neutralizing capacity at 7-14 days following the second dose but equilibrates with the younger cohort after 2-3 months. While long-term vaccination responses remain to be determined, our results implicate vaccine-induced protection in older adults against SARS-CoV-2 variants and inform thinking about boost vaccination.

Developing a Clinical Prototype to Guide Surgeons for Intraoperative Label-Free Identification of Parathyroid Glands in Real Time.

BACKGROUND: Patients undergoing thyroidectomy may have inadvertent damage or removal of the parathyroid gland(s) due to difficulty in real-time parathyroid identification. Near-infrared autofluorescence (NIRAF) has been demonstrated as a label-free modality for intraoperative parathyroid identification with high accuracy. This study presents the translation of that approach into a user-friendly clinical prototype for rapid intraoperative guidance in parathyroid identification. METHODS: A laboratory (lab)-built spectroscopy system that measures NIRAF in tissue was evaluated for identifying parathyroid glands in vivo across 162 patients undergoing thyroidectomy and/or parathyroidectomy. Based on these results, a clinical prototype called PTeye was designed with a user-friendly interface and subsequently investigated in 35 patients. The performance of the lab-built system and the clinical prototype were concurrently compared side by side by a single user with 20 patients in each group. The influence of (i) intrapatient and interpatient variability of NIRAF in thyroid and parathyroid glands and (ii) thyroid and parathyroid pathology on intraoperative parathyroid identification were investigated. The effect of blood on NIRAF intensity of parathyroid and thyroid was tested ex vivo with the PTeye system to assess if a hemorrhagic surgical field would affect parathyroid identification. Accuracy of both systems were determined by correlating the acquired data with either visual confirmation by a surgeon for unexcised parathyroid glands or histology reports for excised parathyroid glands. RESULTS: The overall accuracy of the lab-built system in guiding parathyroid identification was 92.5%, while the PTeye system achieved an accuracy of 96.1%. Unlike the lab-built system, the PTeye could guide parathyroid identification even as the operating room lights remained on and required only 25% of the laser power used by the lab-built setup. Parathyroid glands had elevated NIRAF intensity compared to thyroid and other neck tissues, regardless of thyroid or parathyroid pathology. Blood did not seem to affect tissue NIRAF measurements obtained with both systems. CONCLUSION: In this study, the clinical prototype PTeye demonstrated high accuracy for label-free intraoperative parathyroid identification. The intuitive interface of the PTeye that can guide in identifying parathyroid tissue in the presence of ambient room lights suggests that it is a reliable and easy-to-use tool for surgical personnel.

Label-free intraoperative parathyroid localization with near-infrared autofluorescence imaging.

CONTEXT: The inability to accurately localize the parathyroid glands during parathyroidectomy and thyroidectomy procedures can prevent patients from achieving postoperative normocalcemia. There is a critical need for an improved intraoperative method for real-time parathyroid identification. OBJECTIVE: The objective of the study was to test the accuracy of a real-time, label-free technique that uses near-infrared (NIR) autofluorescence imaging to localize the parathyroid. SETTING: The study was conducted at the Vanderbilt University endocrine surgery center. SUBJECTS AND METHODS: Patients undergoing parathyroidectomy and/or thyroidectomy were included in this study. To validate the intrinsic fluorescence signal in parathyroid, point measurements from 110 patients were collected using NIR fluorescence spectroscopy. Fluorescence imaging was performed on 6 patients. Imaging contrast is based on a previously unreported intrinsic NIR fluorophore in the parathyroid gland. The accuracy of fluorescence imaging was analyzed in comparison with visual assessment and histological findings. MAIN OUTCOME MEASURE: The detection rate of parathyroid glands was measured. RESULTS: The parathyroid glands in 100% of patients measured with fluorescence imaging were successfully detected in real time. Fluorescence images consistently showed 2.4 to 8.5 times higher emission intensity from the parathyroid than surrounding tissue. Histological validation confirmed that the high intrinsic fluorescence signal in the parathyroid gland can be used to localize the parathyroid gland regardless of disease state. CONCLUSION: NIR fluorescence imaging represents a highly sensitive, real-time, label-free tool for parathyroid localization during surgery. The elegance and effectiveness of NIR autofluorescence imaging of the parathyroid gland makes it highly attractive for clinical application in endocrine surgery.

A novel optical approach to intraoperative detection of parathyroid glands.

BACKGROUND: Inadvertent removal of parathyroid glands is a challenge in endocrine operations. There is a critical need for a diagnostic tool that provides sensitive, real-time parathyroid detection during procedures. We have developed an intraoperative technique using near-infrared (NIR) fluorescence for in vivo, real-time detection of the parathyroid regardless of its pathologic state. METHODS: NIR fluorescence was measured intraoperatively from 45 patients undergoing parathyroidectomy and thyroidectomy. Spectra were measured from the parathyroid and surrounding neck tissues during the operation with the use of a portable, probe-based fluorescence system at 785-nm excitation. Accuracy was evaluated by comparison with histology or visual recognition by the surgeon. RESULTS: NIR fluorescence detected the parathyroid in 100% of patients. Parathyroid fluorescence was stronger (1.2-18 times) than that of the thyroid with peak fluorescence at 822 nm. Surrounding tissues showed no auto-fluorescence. Disease state did not affect the ability to discriminate parathyroid glands but may account for signal variability. CONCLUSION: NIR fluorescence spectroscopy can detect intraoperatively the parathyroid regardless of tissue pathology. The signal may be caused by calcium-sensing receptors present in the parathyroid. The signal strength and consistency indicates the simplicity and effectiveness of this method. Its implementation may limit operative time, decrease costs, and improve operative success rates.

New generation of ensemble-decision aliquot ranking based on simplified microfluidic components for large-capacity trapping of circulating tumor cells.

Ensemble-decision aliquot ranking (eDAR) is a sensitive and high-throughput method to analyze circulating tumor cells (CTCs) from peripheral blood. Here, we report the next generation of eDAR, where we designed and optimized a new hydrodynamic switching scheme for the active sorting step in eDAR, which provided fast cell sorting with an improved reproducibility and stability. The microfluidic chip was also simplified by incorporating a functional area for subsequent purification using microslits fabricated by standard lithography method. Using the reported second generation of eDAR, we were able to analyze 1 mL of whole-blood samples in 12.5 min, with a 95% recovery and a zero false positive rate (n = 15).

Perioperative care for the older outpatient undergoing ambulatory surgery.

As the number of ambulatory surgery procedures continues to grow in an aging global society, the implementation of evidence-based perioperative care programs for the elderly will assume increased importance. Given the recent advances in anesthesia, surgery, and monitoring technology, the ambulatory setting offers potential advantages for elderly patients undergoing elective surgery. In this review article we summarize the physiologic and pharmacologic effects of aging and their influence on anesthetic drugs, the important considerations in the preoperative evaluation of elderly outpatients with coexisting diseases, the advantages and disadvantages of different anesthetic techniques on a procedural-specific basis, and offer recommendations regarding the management of common postoperative side effects (including delirium and cognitive dysfunction, fatigue, dizziness, pain, and gastrointestinal dysfunction) after ambulatory surgery. We conclude with a discussion of future challenges related to the growth of ambulatory surgery practice in this segment of our surgical population. When information specifically for the elderly population was not available in the peer-reviewed literature, we drew from relevant information in other ambulatory surgery populations.

Small bowel adenocarcinoma complicating Crohn's disease: case series and review of the literature.

Colonic adenocarcinoma frequently complicates inflammatory bowel disease of the colon, but small bowel adenocarcinoma (SBA) is a rare complication of Crohn's disease (CD). We present two patients with SBA in CD and review the literature with regards to CD-related SBA. A 45-year-old male with a 17-year history of ileal CD presented with obstructive symptoms but no radiographic evidence of a mass. After laparoscopic ileocolectomy and repair of incidental ileosigmoid fistula, pathology showed a T3N0 adenocarcinoma within the ileal CD. Two years after his resection he was without evidence of disease. A 59-year-old male with a 15-year history of CD presented with an acute exacerbation. Small bowel follow through demonstrated a long ileal stricture for which he underwent an ileocolic resection. Postoperative pathology confirmed a T3N1 CD-related SBA. He died from metastatic cancer 3 months later. Review of the literature identified 154 cases of SBA complicating CD with several distinguishing features from de novo SBA. Patients with SBA and CD are, as a group, younger and more likely to be male. SBA is rarely diagnosed preoperatively in these patients, and has a poor prognosis due to its advanced stage at diagnosis.

Mutations in DNA polymerase eta are not detected in squamous cell carcinoma of the skin.

The major etiological agent in skin cancer is exposure to UV-irradiation and the concomitant DNA damage. UV-induced DNA lesions, such as thymine dimers, block DNA synthesis by the major DNA polymerases and inhibit the progression of DNA replication. Bypass of thymine dimers and related lesions is dependent on the translesion polymerase DNA polymerase eta (Poleta). In the inherited disorder, xeroderma pigmentosum variant (XPV), inactivation of Poleta results in extreme sensitivity to UV light and a marked increase in the incidence of skin cancer. Here, we tested the hypothesis that somatic mutations and/or polymorphisms in the POLH gene that encodes Poleta are associated with the induction of UV-dependent skin cancers. We sequenced the exonic regions of the Poleta open reading frame in DNA from 17 paired samples of squamous cell skin carcinoma and adjacent histologically normal tissue. We analyzed approximately 120,000 nucleotides and detected no mutations in POLH in the tumors. However, we identified 6 different single-nucleotide polymorphisms, 3 of them previously undocumented, which were present in both the tumor and paired normal tissue. We conclude that neither mutations nor polymorphisms in the coding regions of POLH are required for the generation of human skin squamous cell carcinoma.