ALVR109, an off-the-shelf partially HLA matched SARS-CoV-2-specific T cell therapy, to treat refractory severe COVID-19 pneumonia in a heart transplant patient: Case report.

An unvaccinated adult male heart transplant recipient patient with recalcitrant COVID-19 due to SARS-CoV-2 delta variant with rising nasopharyngeal quantitative viral load was successfully treated with ALVR109, an off-the-shelf SARS-CoV-2-specific T cell therapy. Background immunosuppression included 0.1 mg/kg prednisone, tacrolimus, and mycophenolate mofetil 1 gm twice daily for historical antibody-mediated rejection. Prior therapies included remdesivir, corticosteroids, and tocilizumab, with requirement for high-flow nasal oxygen. Lack of clinical improvement and acutely rising nasopharyngeal viral RNA more than 3 weeks into illness prompted the request of ALVR109 through an emergency IND. The day following the first ALVR109 infusion, the patient's nasopharyngeal SARS-CoV-2 RNA declined from 7.43 to 5.02 log10 RNA copies/ml. On post-infusion day 4, the patient transitioned to low-flow oxygen. Two subsequent infusions of ALVR109 were administered 10 and 26 days after the first; nasopharyngeal SARS-CoV-2 RNA became undetectable on Day 11, and he was discharged the following day on low-flow oxygen 5 weeks after the initial diagnosis of COVID-19. The clinical and virologic improvements observed in this patient following administration of ALVR109 suggest a potential benefit that warrants further exploration in clinical trials.

Patterns of recurrence after sentinel lymph node biopsy for cutaneous melanoma.

BACKGROUND: Previous sentinel lymph node (SLN) studies for cutaneous melanoma have shown that the SLN accurately reflects the nodal status of the corresponding nodal basin. However, there are few long-term studies that describe recurrence site patterns, predictors for recurrence, and overall survival and disease-free survival after SLN biopsy. METHODS: A retrospective review of patients over a 6-year period was performed to determine patient outcomes and the patterns of recurrence. In all cases, Tc-99 sulfur colloid along with isosulfan blue dye was injected at the primary melanoma site. After resection, the SLN was serially sectioned and evaluated by hematoxylin and eosin staining and immunohistochemistry. RESULTS: One hundred ninety-eight patients were identified who underwent SLN biopsy for cutaneous melanoma including T1 (n = 21), T2 (n = 88), T3 (n = 75), and T4 (n = 14) primary tumors. Of these patients, 38 had a positive SLN. Of the 38 patients with a positive SLN (mean follow-up 38 months), recurrent disease was identified in 10 (26.3%) at a mean interval of 14.2 months. The site of first recurrence was distant (n = 4) and local (n = 6). Regional lymphatic basin recurrence was not identified. Of the 160 patients with a negative SLN (mean follow-up 50 months), recurrent disease was identified in 16 (10.0%) at a mean interval of 31.3 months. The site of first recurrence was systemic (n = 11), local (n = 4), and nodal (n = 1). Overall survival and disease-free survival for patients with a positive SLN at 55 months was 53.3% and 47.7% respectively, while overall survival and disease-free survival for patients with a negative SLN at 53 months was 92.2% and 87.7% respectively (P <0.01). Univariate and multivariate analysis of the entire cohort (n = 198) identified primary tumor depth and positive SLN status as significant predictors of recurrence. CONCLUSIONS: The incidence of nodal basin recurrence after SLN biopsy was found to be 0.6%. Primary tumor depth and pathological status of the SLN are significant predictors of local and systemic recurrence. Long-term follow-up indicates that patients with a positive SLN clearly recur sooner and have decreased overall survival than those with a negative SLN.

Patterns of drainage and recurrence following sentinel lymph node biopsy for cutaneous melanoma of the head and neck.

OBJECTIVES: To analyze lymphatic drainage patterns and recurrence patterns in patients undergoing sentinel lymph node biopsy (SLNB) for cutaneous head and neck melanoma. DESIGN: Retrospective review of a consecutive series with a mean follow-up of 35 months. SETTING: Tertiary cancer care center. PATIENTS: Fifty-one patients with clinically node-negative cutaneous melanoma of the head and neck region staged by means of SLNB. INTERVENTIONS: Sentinel lymph nodes (SLNs) were identified using preoperative lymphatic mapping along with intraoperative gamma probe evaluation and isosulfan blue dye injection. Patients with a positive SLNB finding by hematoxylin-eosin or immunohistochemical evaluation underwent completion lymphadenectomy of the affected lymphatic basin and were considered for further adjuvant treatment. Patients with a negative SLNB finding were observed clinically. MAIN OUTCOME MEASURES: Location characteristics of SLNs, incidence of positive SLNs, same-basin recurrence, and disease-free survival. RESULTS: The mean number of SLNs per patients was 2.75. The extent of SLNB included removal of 1 node (n = 11), multiple nodes from 1 basin (n = 18), 1 node in multiple basins (n = 7), and multiple nodes in multiple basins (n = 15). Drainage to unexpected basins was found in 13 of 51 patients. Parotid region drainage was identified in 18 patients. There were no same-basin recurrences in patients with a negative SLNB finding. Thirty-six-month disease-free survival was 88.9% for patients with a negative SLN and 72.9% for patients with a positive SLN (P=.17). CONCLUSIONS: The number and location of SLNs is variable and difficult to predict for head and neck cutaneous melanoma. Preoperative lymphoscintigraphy is an important planning instrument to guide complete removal of all SLNs. Based on 3-year follow-up, this procedure can be expected to provide low same-basin recurrence rates for patients with a negative SLN.

Surgical weight loss >65 years old: is it worth the risk?

BACKGROUND: Weight loss surgery in patients >65 years old has been underused, secondary to the morbidity and mortality concerns of healthcare providers. Comparative outcomes analyses of this patient population have been lacking. The purpose of the present report was to evaluate the safety and outcome of gastric bypass in patients >65 years of age. METHODS: A prospective database was used to analyze the safety, operative morbidity, and outcome. All patients undergoing surgery since January 2005 were included. RESULTS: The analysis of 1474 patients demonstrated a greater operative risk profile for patients >65 years (n = 100) compared with those <65 years old (n = 1374) related to sleep apnea (45% versus 34%), diabetes mellitus (65% versus 33%), and hypertension (81% versus 57%). The operative outcomes were similar for the 2 groups as determined by the operative time (70 versus 65 minutes), length of stay (1.97 versus 1.3 days), and 30-day readmission rate (6.0% versus 7.4%). The postoperative complication rates were low in the patients >65 years old (bleeding 1.0%, pulmonary 3.0%, cardiac 2.0%, wound 2.0%, and 30-day mortality rate 0%). The percentage of excess body weight loss in the gastric bypass patients was similar between the patients >65 years old and those <65 years old at 12 months (74.8% versus 77.8%) and 24 months (83.4% versus 78.5%). CONCLUSION: Our experience represents one of the largest series of laparoscopic gastric bypass in elderly patients. The data have demonstrated excellent outcomes compared with a younger population.

Optimizing outcomes in bariatric surgery: outpatient laparoscopic gastric bypass.

BACKGROUND: Roux-en-Y gastric bypass (RYGB) is an effective treatment of severe obesity and one of the fastest growing surgical procedures in the United States. METHODS: A single institution prospective database of patients undergoing outpatient laparoscopic (lap) RYGB over a 3-year period was reviewed. Study end points included hospital discharge within 23 hours, 30-day hospital readmission rate, early (<30 day) and late complication rates, and 30-day perioperative mortality. Variables assessed included surgeon experience, patient demographics, comorbidities, operative time, Roux limb pathway, intraoperative steroid bolus, and use of dexmedetomidine. RESULTS: Two thousand consecutive patients undergoing outpatient lap RYGB were identified, and 84% (n = 1669) were discharged within 23 hours. Of these, 1.7% (n = 34) were readmitted within 30 days. The overall early and late complication rates were 1.9% (n = 38) and 4.3% (n = 86), respectively. The 30-day mortality rate was 0.1% (n = 2), and neither patient was discharged before death. Univariate analysis demonstrated surgeon experience (<50 cases), age (<56 years), body mass index (<60 kg/m), weight (400 lbs), comorbidities (<5), and intraoperative steroid bolus as predictive of successful outpatient discharge. Multivariate analysis revealed surgeon experience, comorbidities, body mass index, and steroid bolus as predictive variables. CONCLUSIONS: These data suggest that outpatient lap RYGB can be performed with acceptable perioperative complication rates, hospital readmission, and mortality rates. Surgeon experience, careful patient selection, and the use of intraoperative steroid bolus predicted optimal patient outcomes.