Factors Associated with Revision Surgery after Internal Fixation of Hip Fractures

Background: Femoral neck fractures are associated with high rates of revision surgery after management with internal fixation. Using data from the Fixation using Alternative Implants for the Treatment of Hip fractures (FAITH) trial evaluating methods of internal fixation in patients with femoral neck fractures, we investigated associations between baseline and surgical factors and the need for revision surgery to promote healing, relieve pain, treat infection or improve function over 24 months postsurgery. Additionally, we investigated factors associated with (1) hardware removal and (2) implant exchange from cancellous screws (CS) or sliding hip screw (SHS) to total hip arthroplasty, hemiarthroplasty, or another internal fixation device. Methods: We identified 15 potential factors a priori that may be associated with revision surgery, 7 with hardware removal, and 14 with implant exchange. We used multivariable Cox proportional hazards analyses in our investigation. Results: Factors associated with increased risk of revision surgery included: female sex, [hazard ratio (HR) 1.79, 95% confidence interval (CI) 1.25-2.50; P = 0.001], higher body mass index (fo

Re-induction ipilimumab following acquired resistance to combination ipilimumab and anti-PD-1 therapy.

Combination immunotherapy with nivolumab and ipilimumab has a high initial response rate in advanced melanoma; however, up to 55% of patients later progress. The efficacy and safety of ipilimumab re-induction in the setting of acquired resistance (AR) to combination immunotherapy is unknown. Patients with advanced melanoma who initially achieved a complete response, partial response or sustained stable disease to induction combination immunotherapy then progressed and were reinduced with ipilimumab (alone or in combination with anti-PD-1) and were analysed retrospectively. Demographics, disease characteristics, efficacy and toxicity were examined. Forty-seven patients were identified from 12 centres. The response rate to reinduction therapy was 12/47 (26%), and disease control rate was 21/47 (45%). Responses appeared more frequent in patients who developed AR after ceasing induction immunotherapy (30% vs. 18%, P = 0.655). Time to AR was 11 months (95% confidence interval [CI], 8-15 months). After a median follow-up of 16 months (95% CI, 10-25 months), responders to reinduction had a median progression-free survival of 14 months (95% CI, 13, NR months), and in the whole cohort, the median overall survival from reinduction was 17 months (95% CI, 12-NR months). Twenty-seven (58%) immune-related adverse events (irAEs) were reported; 18 (38%) were grade 3/4, and in 11 of 27 (40%), the same irAE observed during induction therapy recurred. Reinduction with ipilimumab ± anti-PD-1 has modest clinical activity. Clinicians should be attentive to the risk of irAEs, including recurrence of irAEs that occurred during induction therapy. Future studies are necessary to determine best management after resistance to combination immunotherapy

Ipilimumab alone or ipilimumab plus anti-PD-1 therapy in patients with metastatic melanoma resistant to anti-PD-(L)1 monotherapy: a multicentre, retrospective, cohort study.

Anti-PD-1 therapy (hereafter referred to as anti-PD-1) induces long-term disease control in approximately 30% of patients with metastatic melanoma; however, two-thirds of patients are resistant and will require further treatment. We aimed to determine the efficacy and safety of ipilimumab plus anti-PD-1 (pembrolizumab or nivolumab) compared with ipilimumab monotherapy in patients who are resistant to anti-PD-(L)1 therapy (hereafter referred to as anti-PD-[L]1). This multicentre, retrospective, cohort study, was done at 15 melanoma centres in Australia, Europe, and the USA. We included adult patients (aged ≥18 years) with metastatic melanoma (unresectable stage III and IV), who were resistant to anti-PD-(L)1 (innate or acquired resistance) and who then received either ipilimumab monotherapy or ipilimumab plus anti-PD-1 (pembrolizumab or nivolumab), based on availability of therapies or clinical factors determined by the physician, or both. Tumour response was assessed as per standard of care (CT or PET-CT scans every 3 months). The study endpoints were objective response rate, progression-free survival, overall survival, and safety of ipilimumab compared with ipilimumab plus anti-PD-1. We included 355 patients with metastatic melanoma, resistant to anti-PD-(L)1 (nivolumab, pembrolizumab, or atezolizumab), who had been treated with ipilimumab monotherapy (n=162 [46%]) or ipilimumab plus anti-PD-1 (n=193 [54%]) between Feb 1, 2011, and Feb 6, 2020. At a median follow-up of 22·1 months (IQR 9·5-30·9), the objective response rate was higher with ipilimumab plus anti-PD-1 (60 [31%] of 193 patients) than with ipilimumab monotherapy (21 [13%] of 162 patients; p<0·0001). Overall survival was longer in the ipilimumab plus anti-PD-1 group (median overall survival 20·4 months [95% CI 12·7-34·8]) than with ipilimumab monotherapy (8·8 months [6·1-11·3]; hazard ratio [HR] 0·50, 95% CI 0·38-0·66; p<0·0001). Progression-free survival was also longer with ipilimumab plus anti-PD-1 (median 3·0 months [95% CI 2·6-3·6]) than with ipilimumab (2·6 months [2·4-2·9]; HR 0·69, 95% CI 0·55-0·87; p=0·0019). Similar proportions of patients reported grade 3-5 adverse events in both groups (59 [31%] of 193 patients in the ipilimumab plus anti-PD-1 group vs 54 [33%] of 162 patients in the ipilimumab group). The most common grade 3-5 adverse events were diarrhoea or colitis (23 [12%] of 193 patients in the ipilimumab plus anti-PD-1 group vs 33 [20%] of 162 patients in the ipilimumab group) and increased alanine aminotransferase or aspartate aminotransferase (24 [12%] vs 15 [9%]). One death occurred with ipilimumab 26 days after the last treatment: a colon perforation due to immune-related pancolitis. In patients who are resistant to anti-PD-(L)1, ipilimumab plus anti-PD-1 seemed to yield higher efficacy than ipilimumab with a higher objective response rate, longer progression-free, and longer overall survival, with a similar rate of grade 3-5 toxicity. Ipilimumab plus anti-PD-1 should be favoured over ipilimumab alone as a second-line immunotherapy for these patients with advanced melanoma. None

Fermentação ruminal e eficiência microbiana em bezerros holandeses alimentados com dietas contendo diferentes níveis de concentrado Ruminal fermentation and microbial efficiency in Holstein calves fed diets with different concentrate levels

RESUMO - Este trabalho foi realizado para avaliar os efeitos de diferentes níveis de concentrado sobre os parâmetros da fermentação ruminal, as digestibilidades aparente, total, ruminal e intestinal de N, a eficiência microbiana e o balanço de N. Cinco bezerros holandeses, inteiros, fistulados no rúmen e abomaso, com idade média inicial de 5,8±0,7 meses e 107,4±11,0 kg PV médio inicial, foram distribuídos em quadrado latino 5x5 (tratamento x período). Os animais foram alojados em baias individuais e alimentados à vontade com dietas contendo 30,0; 45,0; 60;0; 75,0; e 90,0% de concentrado, com base na MS, em rações contendo como volumoso, o feno de capim coast-cross e no concentrado, o farelo de soja, fubá de milho. Os valores de pH foram influenciados pelos níveis de concentrado das rações, e , 11,3 horas após a alimentação, foram estimandos os valores mínimos de 6,10; 5,89; 5,67; 5,46; e 5,24, para as rações com níveis de 30,0; 45,0; 60,0; 75,0; e 90,0%de concentrado nas rações, respectivamente. A concentração de amônia ruminal reduziu linearmente, em função dos tempos pós-alimentação, apresentando comportamento quadrático, com valores mínimos de 6,84; 7,14; 7,63; 7,82; 8,09; e 8,00 mg/dL, para 86,31; 84,86; 83,41; 81,95; 77,59; e 68,86% de concentrado nas rações. O numero de protozoários ruminais reduziu linearmente com o aumento dos níveis de concentrado nas rações. A eficiência de síntese de compostos nitrogenados microbianos aumentou linearmente com os níveis de concentrado nas rações.<br>ABSTRACT - This work was conducted to evaluate the effects of different concentrate levels on the parameters of at ruminal fermentation, the apparent, total, ruminal and intestinal N digestibilities, the microbial efficiency and the N balance. Five rumen and abomasum fistulated bull Holstein calves, with an initial average age of 5.8±0.7 months and initial average of 107.4±11.0 kg LW were allotted to a 5x5 Latin square design (treatment x period). The animals were housed in individual stalls and full fed diets (DM basis) containing 30.0, 45.0, 60.0, 75,0 and 90.0% of concentrate.The diets were based on coast-cross grass hay as forage and soybean meal and corn ground grain in the concentrate. The pH values were affected by the concentrate levels of the diets, and , 11.3 hours post-feeding, the minimum values of 6.10, 5.89, 5.67, 5.46, and 5.24, respectively, were estimated for the diets with 30.0, 45.0, 60.0, 75.0 e 90.0% of concentrate in the diets, respectively. The ruminal ammonia concentration linearly decreased, in function of post-feeding time and showing quadratic behavior, with a minimum values of 6.84, 7.14, 7,40, 7.63, 7.82, 8.09, and 8.00 mg/dL, for 86.31, 84.86, 83.41, 80,50, 81.95, 77.59, and 68.86% of concentrate in the diets. The number of ruminal protozoa linearly reduced as the dietary concentrate levels increased. The efficiency of microbial nitrogenous compound synthesis linearly increased, as the concentrate levels in the diets increased