Cervical Spinal Cord Stimulation for Failed Neck Surgery Syndrome.

PURPOSE OF REVIEW: Cervical spine pain with or without radicular symptoms is a common condition leading to high utilization of the healthcare system with over 10 million medical visits per year. Many patients undergo surgical interventions and unfortunately are still left with neck and upper extremity pain, sometimes referred to as "Failed Neck Surgery Syndrome." When these options fail, cervical spinal cord stimulation can be a useful tool to decrease pain and suffering as well as reduce prescription medication use. RECENT FINDINGS: Spinal cord stimulation is a well-established therapy for chronic back and leg pain and is becoming more popular for neck and upper extremity pain. Recent studies have explored cervical spinal cord stimulation with successful outcomes regarding improved pain scores, functional outcomes, and reduction of prescription medication use. Continued research into cervical spinal cord stimulation is essential for maximizing its therapeutic potential for patients with chronic neck and upper extremity pain. This review highlights the importance of cervical spinal cord stimulation as an option for patients with failed neck surgery syndrome.

Current Review of Regenerative Medicine Therapies for Spine-Related Pain.

PURPOSE OF REVIEW: Persistent spinal pain syndromes are pervasive and lead to functional impairment, increased healthcare utilization, potential disability, and high societal costs. Spinal (cervical, thoracic, lumbar, and sacroiliac joint) pain includes mechanical, degenerative, inflammatory, oncologic, and infectious etiologies. Regenerative medicine is a novel biotechnology targeting mechanical, degenerative, and inflammatory conditions believed to cause pain. Preparations including platelet-rich plasma, mesenchymal stem cells (adipose tissue and bone marrow aspirate concentrates), and growth factors are derived from an autologous donor. The goal of intervention through guided injection of the regenerative media is to reduce inflammation and reverse the degenerative cascade in hopes of restoring normal cellular composition (physiologic homeostasis) and anatomical function to improve pain and function. The authors review limited research supporting the use of platelet-rich plasma injections for facet joint arthropathy and sacroiliac joint pain compared to traditional steroid treatments, as well as the use of platelet rich plasma or mesenchymal stem cells for lumbar discogenic and radicular pain. RECENT FINDINGS: Current evidence to support regenerative medicine for spine-related pain is limited. Although several studies demonstrated a reduction in pain, many of these studies had a small number of participants and were case series or prospective trials. Regenerative medicine treatments lack evidence for the treatment of spine-related pain. Large randomized controlled trials are needed with consistent study protocols to make further recommendations.

Comparing impacts of the COVID-19 pandemic on training of public health Specialty Registrars starting before or after its onset.

Objectives: To capture and compare the differences in experiences of public health Specialty Registrars who commenced training prior to the COVID-19 pandemic (pre-pandemic Registrars) and those who commenced training during the pandemic (post-pandemic Registrars). Study design: This is a mixed methods study comprising a cross-sectional survey and participatory action research. Methods: A questionnaire of 10 open and 5 closed questions exploring participants experience of training during the pandemic was sent to East Midlands Specialty Registrars. Thematic analysis and double coding were undertaken, coded based on pre- or post-pandemic Registrar status. Participatory action research was then undertaken in 2 rounds with 2 groups, based on pre/post-pandemic status to consolidate themes. Results: The survey was completed by 17 Registrars (8 pre-pandemic, and 9 post-pandemic) and 19 Registrars took part in participatory action research. The findings showed pre-pandemic Registrars noted the importance of negative impacts on their mental health whilst post-pandemic Registrars were more positive and felt well supported in their training. Conclusions: There is a stark difference in the impact of the pandemic for Registrars who started training before compared to during the pandemic. The training programme was not resilient to the impact of the pandemic. Robustness could be increased by encouraging early leadership experience and providing wellbeing support, particularly for post pandemic Registrars now and in future.

Initial impact of the COVID-19 pandemic on public health training: participatory action research to understand experiences in the East Midlands.

BACKGROUND: Specialty public health training consists of 48 months of practice across the domains of health protection, healthcare public health and health improvement.With the onset of the COVID-19 pandemic, activity pivoted towards pandemic management and the response became a significant element of registrar practice.This research aimed to understand the impact of this shift in focus on registrars' role and training. METHODS: Participatory action research comprising (i) a reflective survey sent to all specialty registrars in the East Midlands training region and (ii) Delphi rounds with survey respondents to generate consensus and define themes. RESULTS: Sixteen (44%) registrars completed the survey with 12 (75%) participating in the Delphi rounds. The early pandemic response stages both challenged and re-affirmed registrars' role and identity in public health and training while providing unique and diverse learning and development. Underpinning these themes is a variability in experience depending on prior experience, placement and training stage. CONCLUSIONS: The pandemic impacted the practice, training and home-life of registrars who were required to negotiate significant challenge and uncertainty. This original work adds to a growing body of correspondence and opinion pieces articulating the experiences and challenges of medical and public health education during a pandemic.

The prognostic significance of glutamic acid decarboxylase antibodies in patients with chronic pancreatitis undergoing total pancreatectomy with islet autotransplantation.

AIM: Islet autotransplantation (IAT) is considered a 'non-immune' model of islet transplant, with no risk for autoimmune-mediated beta cell loss, but we have previously observed de novo type 1 diabetes in one total pancreatectomy with islet autotransplantation (TPIAT) recipient. We aimed to investigate the clinical significance of glutamic acid decarboxylase antibodies (GADA), as a sensitive marker for autoimmune diabetes mellitus (DM), in patients with chronic pancreatitis undergoing TPIAT. METHODS: We identified 9 patients undergoing TPIAT with elevated GADA pre-TPIAT (8 non-diabetic and 1 with C-peptide positive DM), otherwise demographically similar to GADA negative TPIAT recipients (n=341). Metabolic and clinical measures related to islet cell function were recorded both before and after TPIAT. RESULTS: None of the 9 TPIAT patients achieved insulin independence after surgery, vs. 33% of GADA negative patients (n=318 with 1-yr follow-up). The two patients with the highest titters of GADA (>250 IU/mL) both experienced islet graft failure, despite normoglycaemia pre-TPIAT and high islet mass transplanted (5276 and 9378 IEQ per kg), with elevated HbA1c levels post-TPIAT (8.3%, 9.6%). The remaining 7 seven were insulin dependent with partial graft function and HbA1c levels <7%. CONCLUSION: Insulin dependence was more frequent in 9 patients with elevated GADA prior to TPIAT than in GADA negative TPIAT recipients, with graft failure in 2 cases. We speculate that beta-cell autoimmunity may occur in a small subset of TPIAT recipients and that beta cell antibody testing prior to TPIAT may be warranted to identify individuals at higher risk for insulin dependence.

The effect of lung consolidation, as determined by ultrasonography, on first-lactation milk production in Holstein dairy calves.

Bovine respiratory disease (BRD) is a complex disease process and many reports emphasize the negative implications of clinical BRD in dairy calves. Early diagnosis can be difficult because of inconsistent or absent clinical signs; however, the use thoracic ultrasonography has the potential to improve detection of respiratory disease. Earlier detection of BRD may result in actions to improve calf welfare and production. The objective of this prospective cohort study was to determine if lung consolidation (LC) in young dairy calves influenced age at first calving (AFC), first-lactation milk production, and survival to the end of first lactation. A total of 215 female calves from 3 dairy herds in southwestern Ontario were enrolled and assessed weekly during their first 8 wk of life for evidence of LC using thoracic ultrasonography (Ibex Pro, Loveland, CO). Consolidation was measured, using gridlines on the screen of the ultrasound, in the first 10 intercostal spaces on both sides of the thorax. Calves were considered LC positive if ≥3 cm of consolidated lung was present. Multivariable linear regression models were used to identify risk factors associated with AFC and first-lactation 305-d milk production. A survival analysis was conducted to determine differences in survival from enrolment until the end of first lactation between calves with and without consolidation. In the study population, the following calfhood conditions were detected: twins (4%; n = 8), diarrhea in the first 21 d of life (31%; n = 66), rib fractures (7%; n = 14), lung abscesses (3%; n = 6), and at least one diagnosis of LC (57%; n = 123). Overall, 7% (n = 15) of calves died, and 18% (n = 38) of animals were sold before the end of first lactation. The presence of LC, at least once in the first 8 wk of life, did not influence AFC, but did result in a 525 kg (95% confidence interval: -992.81 to -60.25) decrease in first-lactation 305-d milk production. No difference in survival was detected between LC groups. These results indicate that LC during the first 56 d of life has a long-term effect on dairy calves, manifested as reduced milk production during first lactation.

The Incremental Cost of Incompatible Living Donor Kidney Transplantation: A National Cohort Analysis.

Incompatible living donor kidney transplantation (ILDKT) has been established as an effective option for end-stage renal disease patients with willing but HLA-incompatible living donors, reducing mortality and improving quality of life. Depending on antibody titer, ILDKT can require highly resource-intensive procedures, including intravenous immunoglobulin, plasma exchange, and/or cell-depleting antibody treatment, as well as protocol biopsies and donor-specific antibody testing. This study sought to compare the cost and Medicare reimbursement, exclusive of organ acquisition payment, for ILDKT (n = 926) with varying antibody titers to matched compatible transplants (n = 2762) performed between 2002 and 2011. Data were assembled from a national cohort study of ILDKT and a unique data set linking hospital cost accounting data and Medicare claims. ILDKT was more expensive than matched compatible transplantation, ranging from 20% higher adjusted costs for positive on Luminex assay but negative flow cytometric crossmatch, 26% higher for positive flow cytometric crossmatch but negative cytotoxic crossmatch, and 39% higher for positive cytotoxic crossmatch (p < 0.0001 for all). ILDKT was associated with longer median length of stay (12.9 vs. 7.8 days), higher Medicare payments ($91 330 vs. $63 782 p < 0.0001), and greater outlier payments. In conclusion, ILDKT increases the cost of and payments for kidney transplantation.

Unmethylated Insulin DNA Is Elevated After Total Pancreatectomy With Islet Autotransplantation: Assessment of a Novel Beta Cell Marker.

Beta cell death may occur both after islet isolation and during infusion back into recipients undergoing total pancreatectomy with islet autotransplantation (TPIAT) for chronic pancreatitis. We measured the novel beta cell death marker unmethylated insulin (INS) DNA in TPIAT recipients before and immediately after islet infusion (n = 21) and again 90 days after TPIAT, concurrent with metabolic functional assessments (n = 25). As expected, INS DNA decreased after pancreatectomy (p = 0.0002). All TPIAT recipients had an elevated unmethylated INS DNA ratio in the first hours following islet infusion. In four samples (three patients), INS DNA was also assessed immediately after islet isolation and again before islet infusion to assess the impact of the isolation process: Unmethylated and methylated INS DNA fractions both increased over this interval, suggesting death of beta cells and exocrine tissue before islet infusion. Higher glucose excursion with mixed-meal tolerance testing was associated with persistently elevated INS DNA at day 90. In conclusion, we observed universal early elevations in the beta cell death marker INS DNA after TPIAT, with pronounced elevations in the islet supernatant before infusion, likely reflecting beta cell death induced by islet isolation. Persistent posttransplant elevation of INS DNA predicted greater hyperglycemia at 90 days.

Sitagliptin Treatment After Total Pancreatectomy With Islet Autotransplantation: A Randomized, Placebo-Controlled Study.

Insulin independence after total pancreatectomy and islet autotransplant (TPIAT) for chronic pancreatitis is limited by a high rate of postprocedure beta cell apoptosis. Endogenous glucagon-like peptide-1 and glucose-dependent insulinotropic peptide, which are increased by dipeptidyl peptidase 4 inhibitor therapy (sitagliptin) may protect against beta cell apoptosis. To determine the effect of sitagliptin after TPIAT, 83 adult TPIAT recipients were randomized to receive sitagliptin (n = 54) or placebo (n = 29) for 12 months after TPIAT. At 12 and 18 months after TPIAT, participants were assessed for insulin independence; metabolic testing was performed with mixed meal tolerance testing and frequent sample intravenous glucose tolerance testing. Insulin independence did not differ between the sitagliptin and placebo groups at 12 months (42% vs. 45%, p = 0.82) or 18 months (36% vs. 44%, p = 0.48). At 12 months, insulin dose was 9.0 (standard error 1.7) units/day and 7.9 (2.2) units/day in the sitagliptin and placebo groups, respectively (p = 0.67) and at 18 months 10.3 (1.9) and 7.1 (2.6) units/day, respectively (p = 0.32). Hemoglobin A1c levels and insulin secretory measures were similar in the two groups, as were adverse events. In conclusion, sitagliptin could be safely administered but did not improve metabolic outcomes after TPIAT.

Kidney Exchange to Overcome Financial Barriers to Kidney Transplantation.

Organ shortage is the major limitation to kidney transplantation in the developed world. Conversely, millions of patients in the developing world with end-stage renal disease die because they cannot afford renal replacement therapy-even when willing living kidney donors exist. This juxtaposition between countries with funds but no available kidneys and those with available kidneys but no funds prompts us to propose an exchange program using each nation's unique assets. Our proposal leverages the cost savings achieved through earlier transplantation over dialysis to fund the cost of kidney exchange between developed-world patient-donor pairs with immunological barriers and developing-world patient-donor pairs with financial barriers. By making developed-world health care available to impoverished patients in the developing world, we replace unethical transplant tourism with global kidney exchange-a modality equally benefitting rich and poor. We report the 1-year experience of an initial Filipino pair, whose recipient was transplanted in the United states with an American donor's kidney at no cost to him. The Filipino donor donated to an American in the United States through a kidney exchange chain. Follow-up care and medications in the Philippines were supported by funds from the United States. We show that the logistical obstacles in this approach, although considerable, are surmountable.

Defining the Tipping Point in Surgical Performance for Laparoscopic Donor Nephrectomy Among Transplant Surgery Fellows: A Risk-Adjusted Cumulative Summation Learning Curve Analysis.

The United Network for Organ Sharing recommends that fellowship-trained surgeons participate in 15 laparoscopic donor nephrectomy (LDN) procedures to be considered proficient. The American Society of Transplant Surgeons (ASTS) mandates 12 LDNs during an abdominal transplant surgery fellowship. We performed a retrospective intraoperative case analysis to create a risk-adjusted cumulative summation (RACUSUM) model to assess the learning curve of novice transplant surgery fellows (TSFs). Between January 2000 and December 2014, 30 novice TSFs participated in the organ procurement rotation of our ASTS-approved abdominal transplant surgery fellowship. Measures of surgical performance included intraoperative time, estimated blood loss, and incidence of intraoperative complications. The performance of senior TSFs was used to benchmark novice TSF performance. Scores were tabulated in a learning curve model, adjusting for case complexity and prior TSF case volume. Rates of adverse surgical events were significantly higher for novice TSFs than for senior TSFs. In univariable analysis, multiple renal arteries, high BMI, prior abdominal surgery, male donor, and nephrolithiasis were correlated with higher incidence of adverse surgical events. Based on the RACUSUM model, high intraoperative time is mitigated after 28 procedures, incidence of intraoperative complications tends to diminish after 24 procedures, and improvement in estimated blood loss did not remain consistent. TSFs exhibit a tipping point in LDN performance by 24-28 cases and proficiency by 35-38 cases.

Ultrasound-guided subcostal transversus abdominis plane blocks with liposomal bupivacaine vs. non-liposomal bupivacaine for postoperative pain control after laparoscopic hand-assisted donor nephrectomy: a prospective randomised observer-blinded study.

We compared the effect of subcostal transversus abdominis plane (TAP) block with liposomal bupivacaine to TAP block with non-liposomal bupivacaine on postoperative maximal pain scores in patients undergoing donor nephrectomy. Sixty patients were prospectively randomly assigned to receive ultrasound-guided bilateral TAPs with either 1.3% liposomal bupivacaine and normal saline or 0.25% non-liposomal bupivacaine with adrenaline. There was a significant decrease in maximal pain scores in the liposomal bupivacaine TAP group when compared with the non-liposomal bupivacaine group median (IQR [range]), 24-48 h after injection, 5 (3.0-5.2 [0-10]) vs. 6 (4.5-7.0 [1--9]) p = 0.009; 48-72 h after injection, 3 (2.0-5.0 [0-8]) vs. 5 (3.0-7.0 [0-10]) p = 0.02; and in opioid use 48-72 h after injection, mean (SD) µg equivalents of fentanyl 105 (97) vs. 182 (162) p = 0.03. Liposomal bupivacaine via subcostal TAP infiltration provided superior analgesia up to 72 h after injection when compared with non-liposomal bupivacaine.

HLA-A, -B, -C, -DR, and -DQ Matching in Pancreas Transplantation: Effect on Graft Rejection and Survival.

To enhance selection of appropriate deceased donors for pancreas transplants, we sought to determine whether HLA matching improved posttransplantation outcomes. In this single-center study of 1219 pancreas transplants, we correlated posttransplantation outcomes with HLA-A, -B, -C, -DR, and -DQ matches and mismatches. Rejection was linearly correlated with the number of mismatches. The individual number of HLA mismatches reached significance at four or more with a 2.3- to 2.9-fold increase in rejection. The effect was most predominant with HLA-B (1.8-fold with one mismatch and 2.0-fold with two mismatches) and -DR (1.9-fold with two mismatches) loci, whereas HLA-A, -C, and -DQ matches or mismatches did not independently predict acute rejection. The affect was strongest in solitary pancreas transplants, with little impact for simultaneous pancreas and kidney (SPK). In contrast, HLA matching did not affect graft or patient survival rates but was associated with a reduced risk of opportunistic infection. Avoidance of acute rejection saved an estimated $32 000 for solitary pancreas recipients and $52 000 for SPK recipients in hospital costs. Our data do not support the use of HLA matching for predicting pancreas graft survival but do support its significance for the reduction of acute rejection, particularly for solitary pancreas recipients.

Successful Application of Closed-Loop Artificial Pancreas Therapy After Islet Autotransplantation.

Total pancreatectomy with islet autotransplantation (TPIAT) may relieve the pain of chronic pancreatitis while avoiding postsurgical diabetes. Minimizing hyperglycemia after TPIAT limits beta cell apoptosis during islet engraftment. Closed-loop (CL) therapy combining an insulin pump with a continuous glucose monitor (CGM) has not been investigated previously in islet transplant recipients. Our objective was to determine the feasibility and efficacy of CL therapy to maintain glucose profiles close to normoglycemia following TPIAT. Fourteen adult subjects (36% male; aged 35.9 ± 11.4 years) were randomized to subcutaneous insulin via CL pump (n = 7) or multiple daily injections with blinded CGM (n = 7) for 72 h at transition from intravenous to subcutaneous insulin. Mean serum glucose values were significantly lower in the CL pump group than in the control group (111 ± 4 vs. 130 ± 13 mg/dL; p = 0.003) without increased risk of hypoglycemia (percentage of time <70 mg/dL: CL pump 1.9%, control 4.8%; p = 0.46). Results from this pilot study suggest that CL therapy is superior to conventional therapy in maintaining euglycemia without increased hypoglycemia. This technology shows significant promise to safely maintain euglycemic targets during the period of islet engraftment following islet transplantation.

Development of Autoimmune-Mediated ß Cell Failure After Total Pancreatectomy With Autologous Islet Transplantation.

Total pancreatectomy with islet autotransplantation (TPIAT) is performed for definitive treatment of chronic pancreatitis; patients are not diabetic before surgery, or have C-peptide positive pancreatogenous diabetes. Thus, TPIAT recipients are not traditionally considered at risk for autoimmune loss of the islet graft. We describe a 43-year-old female who underwent TPIAT with high mass islet graft of 6031 IEQ/kg, with no evidence of presurgical ß cell autoimmunity who developed type 1 diabetes within the first year after TPIAT, resulting in complete loss of beta cell function. The patient had positive GAD and insulin autoantibodies at 1 year and 18 months after TPIAT, not present prior, and undetectable C-peptide after mixed meal and intravenous glucose tolerance testing at 18 months. Glucagon secretion was preserved, suggesting the transplanted alpha cell mass was intact. HLA typing revealed a DR3/DR4 class II haplotype. This case highlights the need to consider de novo type 1 diabetes in patients with unexpected islet graft failure after TPIAT.

Defective glucagon secretion during hypoglycemia after intrahepatic but not nonhepatic islet autotransplantation.

Defective glucagon secretion during hypoglycemia after islet transplantation has been reported in animals and humans with type 1 diabetes. To ascertain whether this is true of islets from nondiabetic humans, subjects with autoislet transplantation in the intrahepatic site only (TP/IAT-H) or in intrahepatic plus nonhepatic (TP/IAT-H+NH) sites were studied. Glucagon responses were examined during stepped hypoglycemic clamps. Glucagon and symptom responses during hypoglycemia were virtually absent in subjects who received islets in the hepatic site only (glucagon increment over baseline = 1 ± 6, pg/mL, mean ± SE, n = 9, p = ns; symptom score = 1 ± 1, p = ns). When islets were transplanted in both intrahepatic + nonhepatic sites, glucagon and symptom responses were not significantly different than Control Subjects (TP/IAT-H + NH: glucagon increment = 54 ± 14, n = 5; symptom score = 7 ± 3; control glucagon increment = 67 ± 15, n = 5; symptom score = 8 ± 1). In contrast, glucagon responses to intravenous arginine were present in TP/IAT-H recipients (TP/IAT: glucagon response = 37 ± 8, n = 7). Transplantation of a portion of the islets into a nonhepatic site should be seriously considered in TP/IAT to avoid posttransplant abnormalities in glucagon and symptom responses to hypoglycemia.