Mortality Trends in Geriatric Proximal Femoral Fracture Treatments After National Payor Policy Changes: A National Study.

INTRODUCTION: Proximal femoral fractures (PFFs) are a major medical event in an elderly's life. The extent of conservative treatment is poorly evaluated in Western health systems. This study retrospectively examines a national cohort of patients older than 65 years with PFFs treated by early surgery (ES) (<48h), delayed surgery (DS) (>48h), and conservative treatment (COT) over the past decade (2010 to 2019). RESULTS: The study cohort included 38,841 patients; 18.4% were 65 to 74 years, 41.1% were 75 to 84 years, and 40.5% were older than 85 years; 68.5% were female. ES rose from 68.4% in 2013 to 85% in 2017 ( P < 0.0001). COT dropped from 8.2% in 2010 to 5.2% in 2019 ( P < 0.0001). Level I trauma centers chose 2.3 times less COT (7.75% in 2010 decreased to 3.37% in 2019) while regional hospitals chose COT only 1.4 times less over the years ( P < 0.001). Hospitalization periods differed: 6.3 ± 0.6d for COT, 8.6 ± 0.3d for ES, and 12 ± 0.4d for DS ( P < 0.001), and the in-hospital mortality rates were 10.5%, 2%, and 3.6%, respectively ( P < 0.0001). One-year mortality rates decreased for ES only ( P < 0.001). DISCUSSION: ES rose from 58.1% in 2010 to 84.9% in 2019 ( P = 0.00002). COT is diminishing throughout the Israeli health system, from 8.2% in 2010 to 5.2% in 2019. Tertiary hospitals consistently practice less COT than regional hospitals ( P < 0.001), probably related to surgeons' and anesthetists' appraisal of the patient's medical status and demand. COT had the shortest hospitalization period but carried the highest in-hospital mortality rates (10.5%). The mild difference in out-of-hospital mortality between the COT and DS groups suggests similar patient characteristics that require additional investigation. In conclusion, more PFFs are treated within 48h with a reduced mortality rate, and the 1-year mortality has improved for ES only. Treatment preferences vary between tertiary and regional hospitals.

Immunological effects of heated intraperitoneal chemotherapy can be augmented by thymosin α1.

BACKGROUND: Peritoneal metastases of colorectal carcinoma origin (PM-CRC) are treated by cytoreductive surgery and heated intraperitoneal chemotherapy (HIPEC). However, the majority of patients recur, calling for novel treatments. We explored the immunogenic changes induced by HIPEC and the possibility to use thymosin α1 (Tα1) as an immune-stimulatory agent. METHODS: We used an experimental murine model of PM-CRC combined with mitomycin (MMC)-based HIPEC. We determined immune cell infiltration into tumor metastases after HIPEC administration by means of immunohistochemistry, and determined immunogenic cell death signals in tumor cells by real-time polymerase chain reaction. RESULTS: Mice with PM-CRC treated by HIPEC had increased overall survival (OS) compared to sham-treated mice (median OS 22.8 vs 18.9 days, respectively; P < 0.001). HIPEC induced increased infiltration of CD4+, CD8+, CD68 + and CD20 + cells into omental and visceral metastases at a magnitude of 40-100 %. We searched for potential immune signals induced by HIPEC by determining its effects on known immunogenic cell death proteins (heat-shock protein [HSP]-70, HSP-90 and calreticulin). HIPEC significantly increased HSP-90 mRNA expression (2.37 ± 1.5 vs 1-fold change, P < 0.05). The OS of Tα1 treated mice significantly improved compared to HIPEC-treated mice (16.3 ± 0.8 vs 14.1 ± 0.6 days, respectively, P = 0.02) and vs sham (11.8 ± 0.8 days, P = 0.007). CONCLUSIONS: HIPEC induced immunogenic changes that led to increased immune cell infiltration. These changes were further augmented by Tα1 treatment. Future studies aimed at optimizing Tα1 treatment should focus upon the immune response it evokes.

Thymosin alpha 1 as an adjuvant to hyperthermic intraperitoneal chemotherapy in an experimental model of peritoneal metastases from colonic carcinoma.

INTRODUCTION: Heated intraperitoneal chemotherapy (HIPEC) is currently implemented in the treatment of peritoneal metastases from colorectal carcinoma (PM-CRC) origin. However, recurrence is common and the effectiveness of HIPEC has been questioned. The aim of this study was to evaluate the use of thymosin alpha 1 (Tα1), an immunomodulatory molecule, as an adjuvant to HIPEC treatment. METHODS: We developed an experimental model of HIPEC by the induction of PM-CRC in C57BL mice and intra-abdominal perfusion of mitomycin C (MMC). Mice were treated with Tα1 at 0.6 mg/kg for 5 days after HIPEC. Clinical and immunological parameters were compared between HIPEC and HIPEC + Tα1 groups. RESULTS: Treatment with Tα1 increased overall survival of mice compared to HIPEC treatment alone and sham-treated animals (16.1 ± 0.8 vs. 14.1 ± 0.6 and 11.8 ± 0.8, respectively, p = 0.02). Tα1 had no direct anti-tumor effect, as seen by lack of inhibition of tumor cell proliferation. Tα1 treatment induced a T helper (Th) 1 immune response in tumor metastases as evidenced by a significant increase of the Th1-specific markers IFN-γ and T-bet (1.21 ± 0.3 vs. 0.52 ± 0.08, p < 0.05; 0.88 ± 0.04 vs. 0.64 ± 0.14, p < 0.05, respectively). This Th1 skew was accompanied by increased CD8+ infiltration into omental and visceral metastases by Tα1 treatment compared to sham and HIPEC-treated animals (21.24 ± 2.16 vs. 10.45 ± 0.89 and 7.7 ± 1.3, p < 0.001; 14.12 ± 1.54 vs. 12.12 ± 0.01 and 6.64 ± 0.87, p < 0.01, respectively). CONCLUSIONS: Tα1 augments the effect of HIPEC by the induction of a Th1 anti-tumor immune response. Further experiments should evaluate Tα1 and other novel immunomodulators in order to exploit the immunological opportunities created by HIPEC.

The Impact of the COVID-19 Pandemic on an Israeli Acute Care Surgery Unit: Fewer Patients, More Disease.

BACKGROUND: The COVID-19 pandemic has transformed and affected every aspect of health care. Like any catastrophic event, the stress on hospitals to maintain a certain level of function is immense. Acute surgical pathologies cannot be prevented or curtailed; therefore, it is important to understand patterns and outcomes during catastrophes in order to optimize care and organize the health care system. METHODS: In a single urban tertiary care center, a retrospective study examined the first complete lockdown period of Israel during the COVID-19 pandemic. This was compared to the same time period the previous year. RESULTS: During the pandemic, time to hospitalization was significantly decreased. There was also an overall reduction in surgical admissions yet with a higher percentage being hospitalized for further treatment (69.2% vs 23.5%). The patients admitted during this time had a higher APACHE-II score and Charlson comorbidity index score. During the pandemic, time to surgery was decreased, there were less laparoscopic procedures, and more RBC units were used per patient. There were no differences in overall complications, except when sub-analyzed for major complications (9.7% vs 6.3%). There was no significant difference in overall in-house mortality or morbidity. Length of hospitalization was significantly decreased in the elderly population during the pandemic. CONCLUSION: During the COVID-19 pandemic, despite a significantly less number of patients presenting to the hospital, there was a higher percentage of those admitted needing surgical intervention, and they were overall sicker than the previous year.