Risk Factors and Outcomes of Mucorales Infection in a Modern Cohort of Solid Organ Transplant, Hematopoietic Cell Transplant, and Chimeric Antigen Receptor T-cell Therapy Recipients.

BACKGROUND: Mucorales infections continue to cause significant morbidity and mortality in immunocompromised hosts despite the advent of new approaches for diagnosis and treatment of fungal infections. We aimed to evaluate risk factors and outcomes of Mucorales infection in solid organ transplant, hematopoietic cell transplant, and chimeric antigen receptor T-cell therapy recipients. METHODS: This single-center retrospective study included solid organ transplant, hematopoietic cell transplant, and chimeric antigen receptor T-cell patients with cultures positive for Mucorales. RESULTS: Forty-three patients were included for analysis; 34 solid organ transplant (79%) and 9 hematopoietic stem cell transplant or chimeric antigen receptor T-cell (21%). Infection with Mucorales occurred a median of 184 days after transplant. At the time of diagnosis, 36 patients were on antifungal prophylaxis with the majority receiving posaconazole (53%). Thirty-three had clinically significant disease; 30 received definitive anti-Mucorales therapy and 3 empiric antifungal therapy. Isavuconazole was the most common azole used for treatment in monotherapy recipients. All-cause mortality was 64% and, of these deaths, 18 (75%) were directly related to Mucormycosis. The highest mortality was seen in disseminated and intra-abdominal disease (100%), followed by pulmonary disease (50%). There was no significant association with mortality and transplant type or number of immunosuppressive agents. CONCLUSION: Mucormycosis is an important cause of morbidity and mortality in immunocompromised patients. Breakthrough infection was not uncommon in this study. Data regarding the incidence of infection at approximately 6 months after transplantation can inform prophylaxis and treatment regimens. The spectrum of antifungal regimens used reflects the lack of consensus on ideal regimens for these organisms and a need for more studies.

Risk factors for infection in patients with a failed kidney allograft on immunosuppressive medications.

Patients with a failing kidney allograft are often continued on immunosuppression (IS) to preserve residual kidney function and prevent allosensitization. It has been previously accepted that maintaining patients on immunosuppressive therapy results in an increased risk of infection, hospitalization, and mortality. However, as the management of IS in patients with a failed kidney allograft continues to evolve, it is important to review the data regarding associations between infection and specific immunosuppression regimens. We present a review of the literature of failed kidney allograft management and infection risk, and discuss practices for infection prevention. Fifteen studies, published from 1995 to 2022, which investigated the experience of patients with failed allograft and infection, were identified. Infection was most commonly documented as a general event, but when specified, included infections caused by Candida, Mycobacterium tuberculosis, and Aspergillus. In addition, the definition of reduced "IS" varied from decreased doses of a triple drug regimen to monotherapy, whereas others did not specify which medications patients were receiving. Despite attempts at lowering net immunosuppression, patients with failed allografts remain at risk of acquiring opportunistic and non-opportunistic infections. Although opportunistic infections secondary to IS are expected, somewhat surprisingly, it appears that the greatest risk of infection may be related to complications of dialysis. Therefore, mitigating strategies, such as planning for an arteriovenous (AV) fistula over a hemodialysis catheter placement, may reduce infection risk. Additional studies are needed to provide more information regarding the types and timing of infection in the setting of a failed kidney allograft. In addition, more data are needed regarding specific medications, doses, and timing of taper of IS to guide future patient management and inform strategies for infection surveillance and prophylaxis.

Dual HER2 Suppression with Lapatinib plus Trastuzumab for Metastatic Inflammatory Breast Cancer: A Case Report of Prolonged Stable Disease.

BACKGROUND: Continuous therapy targeting human epidermal growth factor receptor 2 (HER2) is recommended until disease progression for patients with HER2-overexpressing (HER2+) metastatic breast cancer. Prolonged stable disease has been observed with such maintenance therapy using trastuzumab, but the frequency of these cases remains low. Whether combined maintenance therapy with two different HER2-targeted agents could improve the rates of durable progression-free survival compared with trastuzumab alone is under investigation. OBJECTIVES: To evaluate the efficacy of the combined HER2-targeted agents, trastuzumab and lapatinib, as maintenance therapy in one patient. METHODS: We describe a patient with HER2+, hormone receptor-negative, inflammatory metastatic breast cancer who was previously treated with doxorubicin, cyclophosphamide, and zoledronic acid followed by paclitaxel and trastuzumab. After completion, the patient underwent a bilateral mastectomy and then enrolled into a Phase III open-label clinical trial of trastuzumab plus lapatinib. RESULTS: The patient experienced long-term stable disease on combined lapatinib and trastuzumab maintenance therapy over 4 years. CONCLUSIONS: This case demonstrates that prolonged stable disease is possible with lapatinib plus trastuzumab, even in patients with the aggressive inflammatory subtype. Optimization of maintenance therapy could improve outcomes for patients with HER2+ metastatic breast cancer.

Incidence, Risk Factors, and Clinical Outcomes of Incidental Parathyroidectomy During Thyroid Surgery.

BACKGROUND: The reported rate of incidental parathyroidectomy (IP) during thyroid surgery is between 5.2 and 21.6 %. Current literature reports wide discrepancy in incidence, risk factors, and outcomes. Thus study was designed to address definitively the topic of IP and identify associated risk factors and clinical outcomes with this multi-institutional study. METHODS: This retrospective cohort study included 1767 total thyroidectomies that occurred between 1995 and 2014 at two academic centers. Pathologic reports were reviewed for the presence of unintentionally removed parathyroid glands. Demographics, potential risk factors, and postoperative calcium levels were compared with matched control group. Logistic regression, t tests, and Chi squared tests were used when appropriate. RESULTS: IP occurred in 286 (16.2 %) of thyroidectomies. Risk factors for IP were: malignancy, neck dissection, and lymph node metastases (p = 0.005, <0.001, and <0.001). Fifty-three (19.2 %) of IPs were intrathyroidal. Those with IP were more likely to have postoperative biochemical (65.6 vs. 42.0 %; p < 0.001) and symptomatic (13.4 vs. 8.1 %; p = 0.044) hypocalcemia than controls. The number of parathyroids identified intraoperatively was inversely correlated with the number of parathyroid glands in the specimen (p < 0.001). CONCLUSIONS: Our findings indicate that malignancy, lymph node dissection, and metastatic nodal disease are risk factors for IP. Patients with IP were more likely to have postoperative biochemical and symptomatic hypocalcemia than controls, showing that there is a physiologic consequence to IP. Additionally, intraoperative surgeon identification of parathyroid glands results in a lower incidence of IP, highlighting the importance of awareness of parathyroid anatomy during thyroid surgery.

Impact of race on intraoperative parathyroid hormone kinetics: an analysis of 910 patients undergoing parathyroidectomy for primary hyperparathyroidism.

HYPOTHESIS African American patients exhibit different intraoperative parathyroid hormone (IOPTH) profiles than non-African American patients. DESIGN Retrospective review. SETTING University medical center. PATIENTS Nine hundred ten patients who underwent parathyroidectomy for primary hyperparathyroidism between July 2005 and August 2010. INTERVENTIONS All patients underwent preoperative imaging with ultrasonography and sestamibi; operative exploration; and IOPTH measurement at 2 points preexcision and 5 and 10 minutes postexcision. MAIN OUTCOME MEASURES Preexcision and postexcision IOPTH measurements. RESULTS Of the 910 patients, 734 self-reported their race as white (81%); 91, Latino/other (10%); 56, Asian (6%); and 28, African American (3%). African American patients had significantly higher initial preexcision IOPTH levels compared with white patients (348 vs 202 pg/mL; P = .048) and significantly higher 5-minute postexcision IOPTH levels (151 vs 80 pg/mL; P = .01). The 10-minute postexcision IOPTH levels were similar between the 2 groups (52 vs 50 pg/mL). A similar percentage of white and African American patients had a 50% drop in IOPTH level at 10 minutes postexcision. No differences in IOPTH kinetics were observed in the other racial groups examined. CONCLUSIONS African American patients with primary hyperparathyroidism exhibit significantly higher preincision and 5-minute postexcision IOPTH values when compared with white patients. The 10-minute postexcision IOPTH values did not differ between races. The altered IOPTH kinetics identified in African American patients may reflect the severity of biochemical disease but may also be related to genetically predetermined differences in parathyroid hormone metabolism.

Central neck lymph node dissection for papillary thyroid cancer: the reliability of surgeon judgment in predicting which patients will benefit.

BACKGROUND: The role of routine prophylactic central-neck lymph node dissection (CLND) for papillary thyroid cancer (PTC) remains controversial. We perform CLND for PTC only in patients with enlarged nodes as determined by preoperative ultrasound and intraoperative inspection and palpation. METHODS: We identified all patients with PTC who underwent CLND during thyroidectomy (group 1) at our institution, and then we identified an equivalent number of demographically matched patients who underwent thyroidectomy without CLND (group 2) and compared the outcomes of the 2 groups. RESULTS: In all, 191 patients were identified for each group; 49/191 (26%) patients in group 1 developed locoregional nodal recurrence (12% central neck and 21% lateral neck), compared with 11/191 (6%) patients in group 2 (3% central neck and 3% lateral neck; P < .05). Overall, 161/191 (84%) patients in group 1 were disease free at last survey, compared with 180/191 (94%) patients in group 2 (P < .05). Transient hypocalcemia was significantly greater in group 1. No difference was found in disease-specific mortality. CONCLUSION: Surgeon assessment of the central neck compartment is an accurate predictor of which patients with PTC will benefit from CLND. Patients with nonenlarged central neck nodes who undergo total thyroidectomy without CLND have a low risk of developing recurrence.

Central neck lymph node dissection for papillary thyroid cancer: comparison of complication and recurrence rates in 295 initial dissections and reoperations.

BACKGROUND: The American Thyroid Association recently changed its management guidelines for papillary thyroid cancer (PTC) to include routine central neck lymph node dissection (CLND) during thyroidectomy. We currently perform CLND during thyroidectomy only if enlarged central nodes are detected by palpation or ultrasonography; we perform CLND in the reoperative setting for recurrence in previously normal-appearing or incompletely resected nodes. Critics of this approach argue that reoperative CLND has higher complication and recurrence rates than initial CLND. We sought to test this argument, using it as our hypothesis. DESIGN: Retrospective review. SETTING: University hospital. PATIENTS: All patients undergoing CLND for PTC between January 1, 1998, and December 31, 2007. INTERVENTIONS: Thyroidectomy and CLND. MAIN OUTCOME MEASURES: Complications (neck hematoma, recurrent laryngeal nerve injury, and hypoparathyroidism) and recurrence of PTC. RESULTS: Altogether, 295 CLNDs were performed: 189 were initial operations and 106 were reoperations. The rate of transient hypocalcemia (41.8% vs 23.6%) was significantly higher in patients undergoing initial CLND compared with those undergoing reoperative CLND. Rates of neck hematoma (1.1% vs 0.9%), transient hoarseness (4.8% vs 4.7%), permanent hoarseness (2.6% vs 1.9%), and permanent hypoparathyroidism (0.5% vs 0.9%) were not different between initial and reoperative CLND. In addition, recurrence rates in the central (11.6% vs 14.1%) and lateral (21.7% vs 17.0%) compartments were not different between the 2 groups. CONCLUSIONS: Reoperative CLND for PTC has a lower rate of temporary hypocalcemia, the same rate of other complications, and the same rate of recurrence compared with initial CLND. Choosing to observe nonenlarged central neck lymph nodes for PTC does not result in increased complications or recurrence if reoperation is required.