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Summary Background Risk of mortality following surgery in patients across Africa is twice as high as the global average. Most of these deaths occur on hospital wards after the surgery itself. We aimed to assess whether enhanced postoperative surveillance of adult surgical patients at high risk of postoperative morbidity or mortality in Africa could reduce 30-day in-hospital mortality. Methods We did a two-arm, open-label, cluster-randomised trial of hospitals (clusters) across Africa. Hospitals were eligible if they provided surgery with an overnight postoperative admission. Hospitals were randomly assigned through minimisation in recruitment blocks (1:1) to provide patients with either a package of enhanced postoperative surveillance interventions (admitting the patient to higher care ward, increasing the frequency of postoperative nursing observations, assigning the patient to a bed in view of the nursing station, allowing family members to stay in the ward, and placing a postoperative surveillance guide at the bedside) for those at high risk (ie, with African Surgical Outcomes Study Surgical Risk Calculator scores ≥10) and usual care for those at low risk (intervention group), or for all patients to receive usual postoperative care (control group). Health-care providers and participants were not masked, but data assessors were. The primary outcome was 30-day in-hospital mortality of patients at low and high risk, measured at the participant level. All analyses were done as allocated (by cluster) in all patients with available data. This trial is registered with ClinicalTrials.gov , NCT03853824 . Findings Between May 3, 2019, and July 27, 2020, 594 eligible hospitals indicated a desire to participate across 33 African countries; 332 (56%) were able to recruit participants and were included in analyses. We allocated 160 hospitals (13 275 patients) to provide enhanced postoperative surveillance and 172 hospitals (15 617 patients) to provide standard care. The mean age of participants was 37·1 years (SD 15·5) and 20 039 (69·4%) of 28 892 patients were women. 30-day in-hospital mortality occurred in 169 (1·3%) of 12 970 patients with mortality data in the intervention group and in 193 (1·3%) of 15 242 patients with mortality data in the control group (relative risk 0·96, 95% CI 0·69–1·33; p=0·79). 45 (0·2%) of 22 031 patients at low risk and 309 (5·6%) of 5500 patients at high risk died. No harms associated with either intervention were reported. Interpretation This intervention package did not decrease 30-day in-hospital mortality among surgical patients in Africa at high risk of postoperative morbidity or mortality. Further research is needed to develop interventions that prevent death from surgical complications in resource-limited hospitals across Africa. Funding Bill & Melinda Gates Foundation and the World Federati...

Amyloid light-chain (AL) amyloidosis is a multi-organ disease due to deposition of misfolded monoclonal immunoglobulin light chains. IgM AL amyloidosis is a rare variant, about 6% of AL amyloidosis cases, and more data are needed for treatment guidance. In IgM AL amyloidosis, the clonal cell of origin may be a plasma or lymphoplasmacytic cell, and treatments targeting each are employed. We describe presenting clinical and laboratory features of 95 patients with IgM AL amyloidosis treated at Boston University Amyloidosis Center from 1996 to 2012. The median diagnosis age was 66 years (range: 38-89) with 56% males. Organ involvement rates were: kidney (51%); heart (40%); lymph nodes (25%) and gastrointestinal tract (17%). Treatment responses were analyzed for 46 patients seen after 2003. Five treatment regimens were assigned by bone marrow pathology and patient-specific factors. Overall hematologic response rates and very good partial or complete hematologic response rates, respectively, were: high-dose melphalan/stem cell transplant (HDM/SCT) 100%;80%, Bortezomib 82%;27%, Rituximab 80%;27%, immunomodulatory agents (IMids) 75%;0%, and standard dose alkylating agents (Melphalan or cyclophosphamide) 63%;19%. Overall, 5-year survival rates were significantly higher in patients with a hematological response: 79.2 ± 8.5% versus 41 ± 14.9% in non-responders, which is more favorable than typically expected in AL amyloidosis.

Pancreatic cancer is more common in older adults, who are underrepresented in clinical trials and frequently under treated. Chronological age alone should not deter clinicians from offering treatment to geriatric patients, as they are a heterogeneous population. Geriatric assessment, frailty assessment tools, and toxicity risk scores help clinicians select appropriate patients for therapy. For resectable disease, surgery can be safe but should be done at a high-volume center. Adjuvant therapy is important; though there remains controversy on the role of radiation, chemotherapy is well studied and efficacious. In locally advanced unresectable disease, chemoradiation or chemotherapy alone is an option. Neoadjuvant therapy improves the chances of resectability in borderline resectable disease. Chemotherapy extends survival in metastatic disease, but treatment goals and risk-benefit ratios have to be clarified. Adequate symptom management and supportive care are important. There are now many new treatment strategies and novel therapies for this disease.

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AL amyloidosis is a multiorgan disease due to deposition of misfolded monoclonal immunoglobulin light chains. AL amyloidosis associated with IgM paraproteinemia is a rare variant of this disease, constituting approximately 6% of AL amyloidosis cases in the literature. The clonal cell of origin may be a plasma cell or a lymphoplasmacytic cell, and treatments targeting each of these populations have been employed. This study defines the clinical and laboratory characteristics of IgM-related AL amyloidosis patients as well as their response to different therapeutic regimens. We identified 94 patients with IgM-related AL amyloidosis evaluated at the BUMC Amyloidosis Center from 2003 through 2012 for which data was available on 50 who completed treatment. The median age at diagnosis was 65 years (range: 42-79 years) with 31 (62 %) males. The most commonly involved organ was the kidney (59%) followed by heart (37%) and GI tract (22%). The mean IgM was 1049 g/dL (range: 29-9130). The clonal population had lambda light chain restriction in 34 (68%) of patients. Patients were categorized into 5 treatment groups: high-dose melphalan/stem cell transplant (HDM/SCT), bortezomib-based, non-transplant alkylating agents based (melphalan or cyclophosphamide), immunomodulatory agents (IMiDs), and rituximab-based. This grouping was not mutually exclusive. The highest hematologic response rate was observed with HDM/SCT (10/10: 100%), followed by non-transplant alkylating agents (16/22: 73%), bortezomib (7/10: 70%) rituximab (9/13: 69%) then by IMiDs (2/4: 50%). We did not observe an association between positive response to treatment and organ involvement, sex or age at diagnosis. In conclusion, IgM-related ALamyloidosis is an unusual variant of AL amyloidosis. Multiple active therapies with different mechanisms of action exist; treatment should be tailored based upon clinicopathologic and patient-specific factors. Disclosures: Sloan: Millenium: Consultancy.