Sustained Disease Control in Immune Checkpoint Blockade Responders with Microsatellite Instability-high Colorectal Cancer after Treatment Termination.

Immune checkpoint inhibitors improve survival in patients with mismatch repair deficiency/microsatellite instability-high (MSI-H) colorectal cancer. The recurrence outcomes following discontinuation of immunotherapy after prolonged disease control have not been definitively reported in large series. Records from patients with advanced MSI-H colorectal cancer from The University of Texas - MD Anderson Cancer Center who received immunotherapy between 2014 and 2022 and stopped after prolonged clinical benefit were reviewed. Median progression-free and overall survival were estimated. Associations between the event of recurrence and coexisting mutations (KRAS/NRAS, BRAFV600E), metastatic organ involvement (lung, liver, lymph node, or peritoneum), metastatic timing (synchronous vs. metachronous), prior immunotherapy [anti-PD-(L)1 alone or in combination with anti-CTLA antibodies], etiology of MSI status (sporadic vs. hereditary non-polyposis colorectal cancer), and duration of immunotherapy were assessed. Sixty-four patients with MSI-H colorectal cancer without progression on immunotherapy were reviewed. Of these 48 and 16 received anti-PD(L)1 antibody alone or in combination with anti-CTLA-4 antibody, respectively. Median exposure to immunotherapy was 17.6 months (range, 1.3-51.9). After a median follow-up of 22.6 months (range, 0.3-71.7) after stopping immunotherapy, 56 of 64 patients (88%) remained without disease progression. Lung metastases were associated with recurrence/progression (OR, 6.1; P = 0.04), but coexisting mutation, primary tumor sidedness, and immunotherapy were not. These data provide a retrospective, single-institution analysis that showed that most patients with advanced MSI-H colorectal cancer do not recur after treatment cessation, regardless of the reason for stopping treatment or a variety of patient and disease features, supporting an optimistic prognosis of sustained disease control. SIGNIFICANCE: Outcomes for patients with MSI-H colorectal cancer stopping immunotherapy after disease control remain unknown. Sixty-four patients with MSI-H colorectal cancer from our institution stopping treatment for sustained benefit or toxicity were retrospectively assessed. After median follow up of 22 months and median immunotherapy exposure of 18 months, 88% patients remained without progression. All patients who recurred or progressed and were rechallenged with immunotherapy have continued to experience disease control.

Pathogenesis, Clinical Considerations, and Treatments: A Narrative Review on Leprosy.

Hansen disease, known as Leprosy, is an infectious disease caused by Mycobacterium leprae. The disease was once thought to be highly contiguous, and patients with leprosy were treated poorly and had to face discrimination due to the gruesome disease's complications. Mycobacterium leprae, the bacterium causative of leprosy, can generally be found in the nine-banded armadillo. The bacterium is transmitted via aerosol droplets and broken skin-to-skin contact. Once M. leprae enters the body, it will target peripheral nerves and the lining mucosa of the skin and eyes, thus causing inflammation and tenderness of the affected area. Over time, this will lead to peripheral neuropathy and weakness of the affected body parts. Treatment of leprosy involves multi-drug combinations such as dapsone, rifampin, and clofazimine. Even though leprosy is curable, early detection and treatment are crucial to preventing irreversible damage and disabilities. Prevention measures include early detection, treatment regimen adherence, close contact prophylaxis, contact tracing, and community awareness. This review aims to provide the latest diagnostic and therapeutic recommendations for leprosy. It outlines the epidemiology, microbiology, clinical treatment, and immunological methods used to detect leprosy.

In vitro performance assessment of tubular membrane oxygenators.

The definite advantage in oxygen transfer performance of staged (single, double and triple) tubular membrane oxygenators (TMO) is compared with reference to flat membrane oxygenators (Travenol or Landé Edwards). The overall construction of staged TMO with a blood mixing chamber is a very good way to destroy the blood boundary layer and modify the blood stagnant zone in the device. Four sizes of staged TMO were studied using the principle that gases dissolve in water in concentrations linearly proportional to the partial pressures of the gases when in equilibrium with the liquid. The experimental results show that the oxygen transfer rate and the corresponding overall oxygen mass transfer coefficient of staged TMO are increased by the same order as those of the reference membrane oxygenators. Furthermore the essential parameter analysis prove that oxygen transfer increases with the number of stages and decreases with the length of the blood tubular modules. The multistage design of TMO revealed an increase in the hydrodynamic resistance occurring in the apparatus. However the highest relative oxygen transfer efficiency suggests that better fluid distribution as well as better uniformity of oxygenation prevail in the staged devices.