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Background: Positive results from real-time reverse-transcription polymerase chain reaction (rRT-PCR) in recovered patients raise concern that patients who recover from coronavirus disease 2019 (COVID-19) may be at risk of reinfection. Currently, however, evidence that supports reinfection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has not been reported., Methods: We conducted whole-genome sequencing of the viral RNA from clinical specimens at the initial infection and at the positive retest from 6 patients who recovered from COVID-19 and retested positive for SARS-CoV-2 via rRT-PCR after recovery. A total of 13 viral RNAs from the patients' respiratory specimens were consecutively obtained, which enabled us to characterize the difference in viral genomes between initial infection and positive retest., Results: At the time of the positive retest, we were able to acquire a complete genome sequence from patient 1, a 21-year-old previously healthy woman. In this patient, through the phylogenetic analysis, we confirmed that the viral RNA of positive retest was clustered into a subgroup distinct from that of the initial infection, suggesting that there was a reinfection of SARS-CoV-2 with a subtype that was different from that of the primary strain. The spike protein D614G substitution that defines the clade "G" emerged in reinfection, while mutations that characterize the clade "V" (ie, nsp6 L37F and ORF3a G251V) were present at initial infection., Conclusions: Reinfection with a genetically distinct SARS-CoV-2 strain may occur in an immunocompetent patient shortly after recovery from mild COVID-19. SARS-CoV-2 infection may not confer immunity against a different SARS-CoV-2 strain., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Aims: Quorum quenching (QQ) is an attractive strategy for mitigating biofouling in membrane bioreactors (MBRs). However, the effects of QQ on the activated sludge (AS) process have not been adequately evaluated. This study investigated the long-term effects of QQ on a laboratory-scale anoxic-oxic MBR, focusing on AS performance and microbial community., Methods and Results: Anoxic-oxic MBRs with and without QQ were operated for 91 days. QQ did not affect COD and TN removal efficiencies over the experimental period, during which its activity remained >90%. QQ reduced floc size by approximately 8% but had no effect on biomass concentration. AS microbial communities were regularly analysed using massively parallel sequencing. AS bacterial communities were temporally dynamic irrespective of QQ presence, for example, a temporal increase in bacterial diversity and a temporal decay of community similarity. QQ counteracted the temporal change in diversity and the temporal distance-community decay. Community comparison revealed that QQ changed the successional trajectory of the AS community at a late period, because it decelerated temporal changes of specific members, such as Thiothrix and Sphingomonadaceae*. Correlation networks revealed that QQ increased network clustering, complexity and density. The combined results suggest that the tighter microbial association by QQ increased the community resistance., Conclusions: QQ can enhance the diversity and stability of the AS community in MBR by counteracting the innate temporal change in community structure., Significance and Impact of the Study: Our findings are useful for the further advancement of QQ-based strategies in engineered microbial environments., (© 2019 The Society for Applied Microbiology.)

Objective: Evidence for unfavorable outcomes of each type of aggressive variant papillary thyroid carcinoma (AV-PTC) is not clear because most previous studies are focused on tall cell variant (TCV) and did not control for other major confounding factors contributing to clinical outcomes., Design: Retrospective cohort study., Methods: This study included 763 patients with classical PTC (cPTC) and 144 with AV-PTC, including TCV, columnar cell variant (CCV) and hobnail variants. Disease-free survival (DFS) and dynamic risk stratification (DRS) were compared after two-to-one propensity score matching by age, sex, tumor size, lymph node metastasis and extrathyroidal extension., Results: The AV-PTC group had significantly lower DFS rates than its matched cPTC group (HR = 2.16, 95% CI: 1.12-4.16, P  = 0.018). When TCV and CCV were evaluated separately, there was no significant differences in DFS and DRS between patients with TCV ( n  = 121) and matched cPTC. However, CCV group ( n  = 18) had significantly poorer DFS than matched cPTC group (HR = 12.19, 95% CI: 2.11-70.33, P  = 0.005). In DRS, there were significantly more patients with structural incomplete responses in CCV group compared by matched cPTC group ( P  = 0.047). CCV was an independent risk factor for structural persistent/recurrent disease in multivariate analysis (HR = 4.28; 95% CI: 1.66-11.00, P  = 0.001)., Conclusions: When other clinicopathological factors were similar, patients with TCV did not exhibit unfavorable clinical outcome, whereas those with CCV had significantly poorer clinical outcome. Individualized therapeutic approach might be necessary for each type of AV-PTCs., (© 2018 European Society of Endocrinology.)

As there is no effective treatment against hemorrhagic fever with renal syndrome (HFRS), the development of effective vaccine is important. An inactivated hantavirus vaccine (IHV) has been used in Korea, but there has been controversy regarding its effectiveness. We conducted a case-control study to evaluate the vaccine effectiveness (VE) of IHV against HFRS in the Korean military. Unadjusted and adjusted VEs of IHV were 59.1% and 58.9%, respectively. VE was higher in divisions with high incidence of HFRS (unadjusted VE, 71.4%; adjusted VE, 78.7%). Our study demonstrated the moderate effectiveness of IHV in high-risk populations residing in endemic area.

Objective: Active surveillance is an option for patients with papillary thyroid microcarcinoma (PTMC). However, the long-term clinical outcomes after delayed surgery remain unclear. We compared the long-term clinical outcomes of PTMC patients according to the time interval between initial diagnosis and surgery., Design and Methods: In this individual risk factor-matched cohort study, PTMC patients were classified into three groups according to the delay period: ≤6 months, 6-12 months and >12 months. Patients were matched by age, sex, extent of surgery, initial tumor size as measured by ultrasonography (US), and by the presence of extrathyroidal extension, multifocal tumors and central cervical lymph node metastasis. We compared the dynamic risk stratification (DRS) and the development of structural persistent/recurrent disease of patients., Results: A total of 2863 patients were assigned to three groups. Their mean age was 50 years, 81% were female and 66% underwent lobectomy. The mean tumor size at the initial US was 0.63 cm. There were no significant differences in clinicopathological characteristics between groups after individual risk factor matching. Comparison of the DRS revealed no significant difference according to the delay period ( P  = 0.07). During the median 4.8 years of follow-up, there were no significant differences in the development of structural recurrent/persistent disease ( P  = 0.34) and disease-free survival ( P  = 0.25) between groups., Conclusions: In PTMC patients, delayed surgery was not associated with higher risk of structural recurrent/persistent disease compared to immediate surgery. These findings support the notion that surgical treatment can be safely delayed in patients with PTMC under close monitoring., (© 2017 European Society of Endocrinology.)

Context: Papillary thyroid microcarcinoma (PTMC) usually has an excellent prognosis., Objective: To evaluate the three-dimensional structures of PTMCs, using serial neck ultrasonography (US) in patients under active surveillance., Design and Setting: A retrospective cohort study., Participants: In total, 192 patients diagnosed with PTMC under active surveillance for >1 year were included in a median 30-month follow-up. Changes in tumor size were evaluated not only using the maximal tumor diameter but also the tumor volume., Results: The median age of patients was 51.3 years and 145 patients (76%) were female. The median initial maximal tumor diameter and tumor volume were 5.5 mm and 48.8 mm3, respectively. The tumor size increased in 27 patients (14%); 23 patients showed a tumor volume increase >50% without a maximal diameter increase of ≥3 mm. The other four patients had both an increasing tumor volume and increasing maximal tumor diameter ≥3 mm. One patient (0.5%) had newly appeared cervical lymph node (LN) metastasis at 3 years after the initial diagnosis. There were no significant risk factors associated with increased tumor size, such as age, sex, or Hashimoto thyroiditis. Twenty-four patients (13%) underwent delayed thyroid surgery at a median of 31.2 months and seven (29%) had cervical LN metastasis on pathologic examination., Conclusion: Some PTMCs could grow significantly after a relatively short period of active surveillance. We also found that the change in tumor volume was more sensitive to detect tumor progression than the change in the maximal tumor diameter., (Copyright © 2017 Endocrine Society)

Context: Lobectomy is preferred in thyroid cancer to decrease surgical complications and avoid lifelong thyroid-hormone replacement. However, postoperative hypothyroidism, requiring thyroid-hormone replacement, may occur., Objective: We aimed to identify the incidence and risk factors of postoperative hypothyroidism to develop a surveillance strategy after lobectomy for papillary thyroid microcarcinoma (PTMC)., Methods: This historical cohort study involved 335 patients with PTMC treated by lobectomy. Postoperative thyroid functions were measured regularly, and patients were prescribed levothyroxine according to specific criteria. Patients not satisfying hormone-replacement criteria were closely followed up., Results: Postoperative hypothyroidism occurred in 215 patients (64.2%) including 5 (1.5%) with overt hypothyroidism and 210 (62.7%) with subclinical hypothyroidism. Forty patients (11.9%) were required thyroid hormone replacement. One hundred nineteen patients (33.5%) experienced temporary hypothyroidism and spontaneously recovered to euthyroid state. High preoperative thyroid-stimulating hormone (TSH) was the most important factor predicting postoperative hypothyroidism and failure of recover from hypothyroidism (odds ratio [OR], 2.82 and 1.77; 95% confidence interval [CI], 2.07 to 3.95 and 1.22 to 2.63; P < 0.001 and 0.002, respectively). Of the 215 patients eventually developing postoperative hypothyroidism, 70 (32.6%) developed hypothyroidism after the first postoperative year. Postoperative 1-year TSH levels were able to differentiate patients developing late hypothyroidism or euthyroidism (OR, 2.29; 95% CI, 1.68 to 3.26; P < 0.001)., Conclusions: Preoperative and postoperative TSH levels might be predictive for patients who develop postlobectomy hypothyroidism and identify those requiring long-term surveillance for hypothyroidism. Additionally, mild postoperative hypothyroidism cases should be followed up without immediate levothyroxine replacement with the expectation of spontaneous recovery., (Copyright © 2017 by the Endocrine Society)

Background: Irinotecan-based chemotherapy is a standard backbone of therapy in patients with metastatic colorectal cancer (CRC) or gastric cancer (GC). However, there is still a paucity of information concerning the efficacy and safety of irinotecan-based regimens in elderly patients., Patients and Methods: Using the patient cohort ( n  = 1,545) from the UGT1A1 genotype study, we compared the efficacy and safety between elderly and nonelderly patients with metastatic CRC ( n  = 934) or GC ( n  = 611) who received first- or second-line FOLFIRI (irinotecan, leucovorin, and 5-fluorouracil) chemotherapy., Results: Despite lower relative dose intensity in elderly patients, progression-free survival and overall survival were similar between elderly (age ≥70 years) and nonelderly (<70 years) patients in the CRC cohort (hazard ratio [HR], 1.117; 95% confidence interval [CI], 0.927-1.345; p  = .244, and HR, 0.989; 95% CI, 0.774-1.264; p  = .931, respectively) and the GC cohort (HR, 1.093; 95% CI, 0.854-1.400; p  = .479, and HR, 1.188; 95% CI, 0.891-1.585; p  = .241, respectively). In both cohorts, febrile neutropenia (22.1% vs. 14.6% in CRC cohort and 35.2% vs. 22.5% in GC cohort) and asthenia (grade 3: 8.4% vs. 1.7% in CRC cohort and 5.5% vs. 2.9% in GC cohort) were more frequent in elderly patients. In the CRC cohort, mucositis and anorexia were more frequent in elderly patients. In the GC cohort, nausea and vomiting were less frequent in elderly patients., Conclusion: The efficacy of the FOLFIRI regimen was similar between elderly and nonelderly patients in both the CRC and the GC cohorts. However, special attention should be paid to elderly patients because of increased risk for febrile neutropenia and asthenia. The Oncologist 2017;22:293-303 IMPLICATIONS FOR PRACTICE: The efficacy of FOLFIRI (irinotecan, leucovorin, and 5-fluorouracil) chemotherapy in elderly patients with metastatic colorectal cancer or gastric cancer was similar to that in nonelderly patients. However, special attention should be paid to elderly patients because of the increased risk for febrile neutropenia and asthenia. These data suggest that the FOLFIRI regimen could be considered as a standard backbone of therapy in elderly patients with metastatic colorectal cancer or gastric cancer and that the clinical decision between doublet and singlet chemotherapy may not be based solely on age. However, the data require further assessment of frailty and performance status., (© AlphaMed Press 2017.)

Objectives: Crystal-storing histiocytosis (CSH) is an uncommon finding in plasma cell neoplasms. CSH is thought to be an intralysosomal deposition of secreted paraproteins or immunoglobulins, which usually express κ immunoglobulin light chains that finally aggregate in crystals. Because of its rarity, CSH in bone marrow often makes diagnosis difficult., Methods: A 57-year-old woman had IgA κ monoclonal proteinemia and monoclonal proteinuria. In the bone marrow aspirate, plasma cells were initially counted less than what would be expected, whereas histiocytes with intracellular crystals were increased. Then, we used α-naphthyl acetate esterase (ANAE) staining to distinguish between true histiocytes and plasma cells. Immunostaining for κ, CD138, CD56, and CD68 was performed on a bone marrow biopsy specimen., Results: True histiocytes containing crystalline inclusions were stained strongly for ANAE, while unstained cells with intracytoplasmic crystals represented plasma cells. The biopsy specimen revealed diffuse infiltration of CD138-positive plasma cells. We also confirmed the presence of plasma cells, histiocytes, and their crystallized inclusions with the immunostaining. The patient was finally diagnosed with plasma cell myeloma., Conclusions: The diagnosis was challenging; the bone marrow findings resembled features of other histiocytic disorders. The use of immunohistochemistry enabled the diagnosis of CSH in the presence of plasma cell myeloma., (Copyright© by the American Society for Clinical Pathology.)

Background: The purpose of this study was to establish the culture conditions required to isolate, identify and expand male germ stem cell-like cells (GSC-LC) from the testicular tissue of patients with non-obstructive azoospermia (NOA)., Methods and Results: Testicular tissues obtained from patients (two with maturation arrest (MA, n = 2) and Sertoli cell-only syndrome (SCOS, n = 11) were dissociated and plated into gelatin-coated dishes. After 2-4 weeks, cultures from both MA patients (100%) and four SCOS patients (36.3%) exhibited multicellular colonies, which proliferated successfully until passage 10. GSC-LC in the colonies displayed alkaline phosphatase activity, as well as Oct-4 and integrin b1 expression after every passage. After the fifth passage, GSC-LC were differentiated by encapsulation in calcium alginate and further cultivation. At 2 and 6 weeks, cells expressed c-Kit, Scp3, testis-specific histone protein 2B (TH2B), and transition protein (TP)-1. Fluorescence in situ hybridization additionally disclosed a few tetraploid and haploid cells at 6 weeks. Human oocytes were activated in the absence of artificial activation and cleaved after the injection of presumptive spermatids., Conclusions: Our novel culture system may be useful for diagnosing the existence of germ cells and facilitating the treatment of NOA patients.