Australian experience with total pancreatectomy with islet autotransplantation to treat chronic pancreatitis.

BACKGROUND: This study aimed to describe the clinical outcomes of total pancreatectomy with islet autotransplantation (TP-IAT) in Australia. METHODS: Individuals selected for TP-IAT surgery according to the Minnesota Criteria (Appendix) without evidence of diabetes were evaluated including time to transplantation from pancreatectomy, islet numbers infused and post-transplantation HbA1c, C-peptide, total daily insulin and analgesic requirement. RESULTS: Sixteen individuals underwent TP-IAT from Australia and New Zealand between 2010 and 2020. Two recipients are deceased. The median islet equivalents/kg infused was 4244 (interquartile range (IQR) 2290-7300). The median C-peptide 1 month post-TP-IAT was 384 (IQR 210-579) pmol/L and at median 29.5 (IQR 14.5-46.5) months from transplant was 395 (IQR 139-862) pmol/L. Insulin independence was achieved in eight of 15 (53.3%) surviving recipients. A higher islet equivalents transplanted was most strongly associated with the likelihood of insulin independence (P < 0.05). Of the 15 surviving recipients, 14 demonstrated substantial reduction in analgesic requirement. CONCLUSION: The TP-IAT programme in Australia has been a successful new therapy for the management of individuals with chronic pancreatitis including hereditary forms refractory to medical treatment to improve pain management with 50% insulin independence rates.

The scale and dynamics of COVID-19 epidemics across Europe

The number of COVID-19 deaths reported from European countries has varied more than 100-fold. In terms of coronavirus transmission, the relatively low death rates in some countries could be due to low intrinsic (e.g. low population density) or imposed contact rates (e.g. non-pharmaceutical interventions) among individuals, or because fewer people were exposed or susceptible to infection (e.g. smaller populations). Here we develop a flexible empirical model (skew-logistic) to distinguish among these possibilities. We find that countries reporting fewer deaths did not generally have intrinsically lower rates of transmission and epidemic growth, and flatter epidemic curves. Rather, countries with fewer deaths locked down earlier, had shorter epidemics that peaked sooner, and smaller populations. Consequently, as lockdowns are eased we expect, and are starting to see, a resurgence of COVID-19 across Europe. One Sentence SummaryA flexible empirical model shows that European countries reporting fewer COVID-19 deaths locked down earlier, had shorter epidemics that peaked sooner, and smaller populations.

The scale and dynamics of COVID-19 epidemics across Europe.

The number of COVID-19 deaths reported from European countries has varied more than 100-fold. In terms of coronavirus transmission, the relatively low death rates in some countries could be due to low intrinsic (e.g. low population density) or imposed contact rates (e.g. non-pharmaceutical interventions) among individuals, or because fewer people were exposed or susceptible to infection (e.g. smaller populations). Here, we develop a flexible empirical model (skew-logistic) to distinguish among these possibilities. We find that countries reporting fewer deaths did not generally have intrinsically lower rates of transmission and epidemic growth, and flatter epidemic curves. Rather, countries with fewer deaths locked down earlier, had shorter epidemics that peaked sooner and smaller populations. Consequently, as lockdowns were eased, we expected, and duly observed, a resurgence of COVID-19 across Europe.

Tuberculosis epidemics driven by HIV: is prevention better than cure?

OBJECTIVE: To compare the benefits of tuberculosis (TB) treatment with TB and HIV prevention for the control of TB in regions with high HIV prevalence. DESIGN AND METHODS: A compartmental difference equation model of TB and HIV has been developed and fitted to time series and other published data using Bayesian methods. The model is used to compare the effectiveness of TB chemotherapy with three strategies for prevention: highly active antiretroviral therapy (HAART), the treatment of latent TB infection (TLTI) and the reduction of HIV transmission. RESULTS: Even where the prevalence of HIV infection is high, finding and curing active TB is the most effective way to minimize the number of TB cases and deaths over the next 10 years. HAART can be as effective, but only with very high levels of coverage and compliance. TLTI is comparatively ineffective over all time scales. Reducing HIV incidence is relatively ineffective in preventing TB and TB deaths over 10 years but is much more effective over 20 years. CONCLUSIONS: In countries where the spread of HIV has led to a substantial increase in the incidence of TB, TB control programmes should maintain a strong emphasis on the treatment of active TB. To ensure effective control of TB in the longer term, methods of TB prevention should be carried out in addition to, but not as a substitute for, treating active cases.

Uncommon complications of renal transplantation.

As a result of advances in surgical technique and immunosuppressive therapy, the incidence and the consequences of post-transplant surgical complications has decreased. However, surgical complications still cause considerable morbidity and test the skills of the surgical team. Several reviews have been published analyzing the incidence of these complications and the management strategies employed to correct them. We report some uncommon or rare complications encountered in our unit after the introduction of low-dose steroids or steroid-free immunosuppressive protocols.

Phase I trial of the murine monoclonal anti-GD2 antibody 14G2a in metastatic melanoma.

In a phase I trial, 12 patients with GD2 antigen-positive metastatic melanoma received the murine anti-GD2 monoclonal antibody 14G2a. The monoclonal antibody was administered in four doses over an 8-day period with total dose ranging from 10 to 120 mg. All patients receiving greater than 10 mg of 14G2a experienced transient abdominal/pelvic pain during the antibody infusion. Five patients had a delayed extremity pain syndrome following the third and fourth antibody infusion. Four of the five patients developed neurological toxicity, including two patients with significant although reversible motor neuropathy. Two of the patients developed hyponatremia secondary to a syndrome of inappropriate antidiuretic hormone. All 12 patients developed high levels of human anti-14G2a antibody. The plasma half-life of 14G2a was 42 +/- 6 (SD) h. One patient each had a partial response, mixed response, and stable disease, respectively. The very modest antitumor activity accompanied by dose-limiting neurological toxicity at total doses greater than 80 mg may restrict the clinical utility of murine 14G2a.

In-111 labeled monoclonal anti-carcinoembryonic antigen antibody (ZCE025) in the immunoscintigraphic imaging of metastatic antigen-producing adenocarcinomas.

The carcinoembryonic antigen (CEA) is a clinically useful marker since it is expressed by adenocarcinomas of diverse origin. Detection and quantitation of circulating CEA levels is used to follow the clinical course of metastatic adenocarcinoma. In this phase I study, the toxicity, pharmacokinetics, and optimal imaging dose of an In-111 labeled monoclonal anti-CEA antibody (ZCE025) was studied in patients with colorectal carcinoma or any CEA-producing tumor. Twenty-four of 26 evaluable patients (92%) demonstrated at least one site of tumor-specific antibody uptake. Sixty-seven sites of metastatic cancer were identified by conventional diagnostic studies. Twenty-nine (43%) of these sites were demonstrable by radioimmune imaging using ZCE025. Twenty-five additional sites of antibody uptake were observed but could not be associated with metastatic deposits. Lymph node and visceral metastases were visualized more frequently than bone, subcutaneous, lung, or liver metastases. Neither tumor size nor antibody dose (2.5-40 mg) appeared to influence the frequency of tumor imaging. The pharmacokinetics of the In-111 labeled antibody fitted a two-compartment model, and patients receiving less than 10 mg of antibody showed a faster clearance of the antibody than those who received greater than 10 mg.