A Contemporary Review of Cryptorchidism Management in Adults: A Rare Presentation of Bilateral Cryptorchidism Presenting as Pelvic Pain in an Adult Patient.

This case report presents a rare case of adult cryptorchidism, found incidentally in a 25-year-old gentleman who initially presented with abdominal and suprapubic pain and was successfully treated with staged orchidopexy. To our knowledge, to date, our case is the first published instance of bilateral cryptorchidism in an adult presenting with nonspecific suprapubic pain. Cryptorchidism is the most common genital abnormality in newborn boys, and due to its association with an increased risk of infertility and malignancy, current management involves surgical correction with orchidopexy by 12 to 18 months of life. Adult presentation of cryptorchidism is very unusual due to early intervention; therefore, bilateral cryptorchidism is even more rare. As a result, current guidelines do not address proper management for adult cryptorchidism. Therefore, after performing a thorough review of the literature on contemporary guidelines for cryptorchidism management, we aim to highlight our approach to management in this rare case of adult bilateral cryptorchidism. We suggest bilateral orchiectomy as the safest option, if the patient is amendable, or bilateral orchiopexy with long-term follow-up for testicular cancer. Although the American Urological Association guidelines recommend orchiectomy for postpubertal cryptorchid children, currently, no explicit guidelines exist for the preferred method of managing adult cryptorchidism. Due to the increased risk of infertility and testicular cancer with cryptorchidism, orchiectomy instead of orchiopexy may be the preferred surgical approach in some instances. Still, in the case of bilateral cryptorchidism, orchiectomy may not always be the most viable solution, making orchiopexy with long-term follow-up for testicular cancer the best option, such as in our case.

The Role of Mechanotransduction in Contact Inhibition of Locomotion and Proliferation.

Contact inhibition (CI) represents a crucial tumor-suppressive mechanism responsible for controlling the unbridled growth of cells, thus preventing the formation of cancerous tissues. CI can be further categorized into two distinct yet interrelated components: CI of locomotion (CIL) and CI of proliferation (CIP). These two components of CI have historically been viewed as separate processes, but emerging research suggests that they may be regulated by both distinct and shared pathways. Specifically, recent studies have indicated that both CIP and CIL utilize mechanotransduction pathways, a process that involves cells sensing and responding to mechanical forces. This review article describes the role of mechanotransduction in CI, shedding light on how mechanical forces regulate CIL and CIP. Emphasis is placed on filamin A (FLNA)-mediated mechanotransduction, elucidating how FLNA senses mechanical forces and translates them into crucial biochemical signals that regulate cell locomotion and proliferation. In addition to FLNA, trans-acting factors (TAFs), which are proteins or regulatory RNAs capable of directly or indirectly binding to specific DNA sequences in distant genes to regulate gene expression, emerge as sensitive players in both the mechanotransduction and signaling pathways of CI. This article presents methods for identifying these TAF proteins and profiling the associated changes in chromatin structure, offering valuable insights into CI and other biological functions mediated by mechanotransduction. Finally, it addresses unanswered research questions in these fields and delineates their possible future directions.

Identification and partial characterization of new cell density-dependent nucleocytoplasmic shuttling proteins and open chromatin.

The contact inhibition of proliferation (CIP) denotes the cell density-dependent inhibition of growth, and the loss of CIP represents a hallmark of cancer. However, the mechanism by which CIP regulates gene expression remains poorly understood. Chromatin is a highly complex structure consisting of DNA, histones, and trans-acting factors (TAFs). The binding of TAF proteins to specific chromosomal loci regulates gene expression. Therefore, profiling chromatin is crucial for gaining insight into the gene expression mechanism of CIP. In this study, using modified proteomics of TAFs bound to DNA, we identified a protein that shuttles between the nucleus and cytosol in a cell density-dependent manner. We identified TIPARP, PTGES3, CBFB, and SMAD4 as cell density-dependent nucleocytoplasmic shuttling proteins. In low-density cells, these proteins predominantly reside in the nucleus; however, upon reaching high density, they relocate to the cytosol. Given their established roles in gene regulation, our findings propose their involvement as CIP-dependent TAFs. We also identified and characterized potential open chromatin regions sensitive to changes in cell density. These findings provide insights into the modulation of chromatin structure by CIP.

Patient with Adult T-cell Leukemia and Lung Infection caused by Mycobacterium abscessus: Successful Treatment with Intensive Chemotherapy Followed by Haploidentical Hematopoietic Stem Cell Transplantation: A Case Report.

A 63-year-old woman with adult T-cell leukemia (ATL) lymphomatous type developed a mild dry cough. Computed tomography revealed lung lesions with a tree-in-bud appearance during intensive chemotherapy. Antibodies against Mycobacterium avium complex were positive. Bronchoalveolar lavage culture showed growth of M. abscessus complex. Finally, M. abscessus subsp. massiliense was also identified. Sequential use of antimicrobials, including macrolides, was introduced during intensive chemotherapy, and the patient successfully underwent allogeneic hematopoietic stem cell transplantation (AHSCT). This is the first case report of a patient with ATL complicated by M. massiliense lung infection, who was successfully treated with haploidentical AHSCT using various combinations of antimicrobials.

UBE2A/B is the trans-acting factor mediating mechanotransduction and contact inhibition.

Mechanotransduction and contact inhibition (CI) control gene expression to regulate proliferation, differentiation, and even tumorigenesis of cells. However, their downstream trans-acting factors (TAFs) are not well known due to a lack of a high-throughput method to quantitatively detect them. Here, we developed a method to identify TAFs on the cis-acting sequences that reside in open chromatin or DNaseI-hypersensitive sites (DHSs) and to detect nucleocytoplasmic shuttling TAFs using computational and experimental screening. The DHS-proteomics revealed over 1000 potential mechanosensing TAFs and UBE2A/B (Ubiquitin-conjugating enzyme E2 A) was experimentally identified as a force- and CI-dependent nucleocytoplasmic shuttling TAF. We found that translocation of YAP/TAZ and UBE2A/B are distinctively regulated by inhibition of myosin contraction, actin-polymerization, and CI depending on cell types. Next-generation sequence analysis revealed many downstream genes including YAP are transcriptionally regulated by ubiquitination of histone by UBE2A/B. Our results suggested a YAP-independent mechanotransduction and CI pathway mediated by UBE2A/B.

Determination of arterial invasion in pancreatic ductal adenocarcinoma: what is the best diagnostic criterion on CT?

OBJECTIVES: To investigate the diagnostic performance and interobserver variability in the determination of arterial invasion in pancreatic ductal adenocarcinoma (PDAC) and determine the best CT imaging criterion. METHODS: We retrospectively evaluated 128 patients with PDAC (73 men and 55 women) who underwent preoperative contrast-enhanced CT. Five board-certified radiologists (expert) and four fellows (non-expert]) independently assessed the arterial invasion (celiac, superior mesenteric, splenic, and common hepatic arteries) using a 6-point score: 1, no tumor contact; 2, hazy attenuation ≤ 180°; 3, hazy attenuation > 180°; 4, solid soft tissue contact ≤ 180°; 5, solid soft tissue contact > 180°; and 6, contour irregularity. ROC analysis was performed to evaluate the diagnostic performance and determine the best diagnostic criterion for arterial invasion, with pathological or surgical findings as references. Interobserver variability was assessed using Fleiss's ĸ statistics. RESULTS: Among the 128 patients, 35.2% (n = 45/128) received neoadjuvant treatment (NTx). Solid soft tissue contact ≤ 180° was the best diagnostic criterion for arterial invasion as defined by the Youden Index both in patients who did and did not receive NTx (sensitivity, 100% vs. 100%; specificity, 90% vs. 93%; and AUC, 0.96 vs. 0.98, respectively). Interobserver variability among the non-expert was not inferior to that among the expert (ĸ = 0.61 vs 0.61; p = .39 and ĸ = 0.59 vs 0.51; p < .001 in patients treated with and without NTx, respectively). CONCLUSIONS: Solid soft tissue contact ≤ 180° was the best diagnostic criterion for the determination of arterial invasion in PDAC. Considerable interobserver variability was seen among the radiologists. KEY POINTS: • Solid soft tissue contact ≤ 180° was the best diagnostic criterion for the determination of arterial invasion in pancreatic ductal adenocarcinoma. • Interobserver agreement among non-expert radiologists was almost comparable to that among expert radiologists.

Microtubule-associated proteins and enzymes modifying tubulin.

Microtubules (MTs) are essential for many cellular processes including establishment of cell shape and polarity, chromosome segregation, vesicle transport, and nuclear positioning. Human cells express 22 tubulin isoforms that have both overlapping and distinctive functions. Tubulins reversely polymerize to form cylindrical MTs, while MT-associated proteins (MAPs), posttranslational modifications (PTMs), and mechanical forces regulate their functions. To help both tubulin researchers and medicinal chemists, this review article lists 489 MAPs, 43 known enzymes that mediate PTMs, and 306 drugs that influence the functions of MTs and MAPs and discusses recent microtubule research. Readers are able to sort the list based on name, size, functions, related human diseases, and date of discovery. The list also contains links to Uniprot and Protein Atlas databases to access further details such as protein structure, associated proteins, subcellular localization, expression levels in cells and tissues, mutations, and pathology. Because the microtubule cytoskeleton is involved in many pathological processes such as tumorigenesis, invasion, and developmental diseases, small molecules that target on MT and MAPs hold potential to treat these diseases and are also listed.

Radiosurgery fractionation and post-treatment hemorrhage development for intact melanoma brain metastases.

PURPOSE: To assess, for intact melanoma brain metastases (MBM), whether single-fraction stereotactic radiosurgery (SRS) versus fractionated stereotactic radiotherapy (fSRT) is associated with a differential risk of post-treatment lesion hemorrhage (HA) development. METHODS: A single institution retrospective database review identified consecutive patients with previously unresected MBM treated with robotic SRS/fSRT between 2013 and 2021. The presence of lesion HA was determined by multi-disciplinary imaging review. Dosimetric variables were reported as biologically effective doses using an α/ß ratio of 2.5 (BED2.5). Statistical analysis was performed using mixed effect logistic regression for post-treatment HA and Cox frailty modeling for local control (LC). RESULTS: The cohort included 48 patients with 226 intact MBM treated with SRS/fSRT. Of lesions without prior HA, 63 of 133 lesions (47.4%) receiving SRS demonstrated evidence of post-treatment HA versus 2 of 24 lesions (8.3%) treated with fSRT (p = 0.01). A larger maximum BED2.5 was observed in lesions developing HA compared to no HA (238.3 Gy vs. 211.4 Gy; p = 0.022). 12-month LC was 65.7% (95% CI 37.2-87.3%) and 77.5% (95% CI 58.5-91.2%) for lesions demonstrating pre-treatment and post-treatment HA, respectively, with no local failure events observed within 12 months for non-hemorrhagic lesions (p < 0.001). CONCLUSION: We found an increased incidence of post-treatment HA for intact MBM receiving a larger maximum BED2.5, which was significantly higher for single fraction treatments within our cohort. The presence of lesion HA, either pre- or post-treatment, was indicative of inferior LC. Further investigations of optimal dose and fractionation schedules for treatment of MBM in the era of immunotherapy are warranted.

Mental foramen in panoramic radiography can be a reference for discrimination of punched-out lesions in the mandible in patients with symptomatic multiple myeloma: A cross-sectional study.

Multiple myeloma (MM) is a hematopoietic malignancy characterized by monoclonal proliferation of plasma cells. MM features bony radiolucencies called punched-out lesions (POLs), which require appropriate diagnosis due to increased risk of surgically-related adverse events. Although dental surgeons can identify dental focal infections (DFIs) in MM patients, the prevalence and characteristics of POLs in the jawbone of MM patients have not been investigated. We examined the prevalence of POLs in the mandible of MM patients, evaluated its relationship with MM International Staging System progression, and examined panoramic radiographs as a diagnostic reference for POLs in a single center in Japan. We identified 98 patients (55 men, 43 women) with a median age of 63 (range, 34 to 91) years. Of these, 18 patients (18.4%) had POLs in the mandible, including two patients in stage I (2/37; 5.4%), six in stage II (6/43; 14.0%), and ten in stage III (10/18; 55.6%). The prevalence of POLs significantly increased with MM stage progression (p < 0.0001). POLs confirmed on computed tomography (CT) were also detected on panoramic radiographs. The Hounsfield unit value at the site of POLs was nearly the same or lower than that of the mental foramen. Although the prevalence of POLs in the mandible is low, dental surgeons need to differentiate POLs as radiological findings when examining DFIs in MM patients. Confirmation of POLs in the mandible is possible by CT and panoramic radiography, and the mental foramen is likely to be a reference for discrimination.

The role of endoscopy in the management of gastroesophageal reflux disease.

Gastroesophageal reflux disease (GERD) is a common disease that may cause a huge economic burden. Endoscopy is performed not only to rule out other organic diseases but also to diagnose reflux esophagitis or Barrett's esophagus. Non-erosive GERD (non-erosive reflux disease [NERD]) is called endoscopy-negative GERD; however, GERD-related findings could be obtained through histological assessment, image-enhanced endoscopy, and new endoscopic modalities in patients with NERD. Moreover, endoscopy is useful to stratify the risk for the development of GERD. In addition, endoscopic treatments have been developed. These techniques could significantly improve patients' quality of life as well as symptoms.

Actin-Associated Proteins and Small Molecules Targeting the Actin Cytoskeleton.

Actin-associated proteins (AAPs) act on monomeric globular actin (G-actin) and polymerized filamentous actin (F-actin) to regulate their dynamics and architectures which ultimately control cell movement, shape change, division; organelle localization and trafficking. Actin-binding proteins (ABPs) are a subset of AAPs. Since actin was discovered as a myosin-activating protein (hence named actin) in 1942, the protein has also been found to be expressed in non-muscle cells, and numerous AAPs continue to be discovered. This review article lists all of the AAPs discovered so far while also allowing readers to sort the list based on the names, sizes, functions, related human diseases, and the dates of discovery. The list also contains links to the UniProt and Protein Atlas databases for accessing further, related details such as protein structures, associated proteins, subcellular localization, the expression levels in cells and tissues, mutations, and pathology. Because the actin cytoskeleton is involved in many pathological processes such as tumorigenesis, invasion, and developmental diseases, small molecules that target actin and AAPs which hold potential to treat these diseases are also listed.

Deep learning image reconstruction algorithm for pancreatic protocol dual-energy computed tomography: image quality and quantification of iodine concentration.

OBJECTIVES: To evaluate the image quality and iodine concentration (IC) measurements in pancreatic protocol dual-energy computed tomography (DECT) reconstructed using deep learning image reconstruction (DLIR) and compare them with those of images reconstructed using hybrid iterative reconstruction (IR). METHODS: The local institutional review board approved this prospective study. Written informed consent was obtained from all participants. Thirty consecutive participants with pancreatic cancer (PC) underwent pancreatic protocol DECT for initial evaluation. DECT data were reconstructed at 70 keV using 40% adaptive statistical iterative reconstruction-Veo (hybrid-IR) and DLIR at medium and high levels (DLIR-M and DLIR-H, respectively). The diagnostic acceptability and conspicuity of PC were qualitatively assessed using a 5-point scale. IC values of the abdominal aorta, pancreas, PC, liver, and portal vein; standard deviation (SD); and coefficient of variation (CV) were calculated. Qualitative and quantitative parameters were compared between the hybrid-IR, DLIR-M, and DLIR-H groups. RESULTS: The diagnostic acceptability and conspicuity of PC were significantly better in the DLIR-M group compared with those in the other groups (p < .001-.001). The IC values of the anatomical structures were almost comparable between the three groups (p = .001-.9). The SD of IC values was significantly lower in the DLIR-H group (p < .001) and resulted in the lowest CV (p < .001-.002) compared with those in the hybrid-IR and DLIR-M groups. CONCLUSIONS: DLIR could significantly improve image quality and reduce the variability of IC values than could hybrid-IR. KEY POINTS: Image quality and conspicuity of pancreatic cancer were the best in DLIR-M. DLIR significantly reduced background noise and improved SNR and CNR. The variability of iodine concentration was reduced in DLIR.

Adrenal-permissive HSD3B1 genetic inheritance and risk of estrogen-driven postmenopausal breast cancer.

BACKGROUNDGenetics of estrogen synthesis and breast cancer risk has been elusive. The 1245A→C missense-encoding polymorphism in HSD3B1, which is common in White populations, is functionally adrenal permissive and increases synthesis of the aromatase substrate androstenedione. We hypothesized that homozygous inheritance of the adrenal-permissive HSD3B1(1245C) is associated with postmenopausal estrogen receptor-positive (ER-positive) breast cancer.METHODSA prospective study of postmenopausal ER-driven breast cancer was done for determination of HSD3B1 and circulating steroids. Validation was performed in 2 other cohorts. Adrenal-permissive genotype frequency was compared between postmenopausal ER-positive breast cancer, the general population, and postmenopausal ER-negative breast cancer.RESULTSProspective and validation studies had 157 and 538 patients, respectively, for the primary analysis of genotype frequency by ER status in White female breast cancer patients who were postmenopausal at diagnosis. The adrenal-permissive genotype frequency in postmenopausal White women with estrogen-driven breast cancer in the prospective cohort was 17.5% (21/120) compared with 5.4% (2/37) for ER-negative breast cancer (P = 0.108) and 9.6% (429/4451) in the general population (P = 0.0077). Adrenal-permissive genotype frequency for estrogen-driven postmenopausal breast cancer was validated using Cambridge and The Cancer Genome Atlas data sets: 14.4% (56/389) compared with 6.0% (9/149) for ER-negative breast cancer (P = 0.007) and the general population (P = 0.005). Circulating androstenedione concentration was higher with the adrenal-permissive genotype (P = 0.03).CONCLUSIONAdrenal-permissive genotype is associated with estrogen-driven postmenopausal breast cancer. These findings link genetic inheritance of endogenous estrogen exposure to estrogen-driven breast cancer.FUNDINGNational Cancer Institute, NIH (R01CA236780, R01CA172382, and P30-CA008748); and Prostate Cancer Foundation Challenge Award.

CT and MRI Findings of Focal Splenic Lesions and Ascites in Generalized Lymphatic Anomaly, Kaposiform Lymphangiomatosis, and Gorham-Stout Disease.

OBJECTIVES: This study aimed to evaluate the CT and MRI findings of focal splenic lesions and ascites in generalized lymphatic anomaly (GLA), kaposiform lymphangiomatosis (KLA), and Gorham-Stout disease (GSD). MATERIAL AND METHODS: Twenty-three patients (10 with GLA, 5 with KLA, and 8 with GSD) who underwent abdominal CT and/or MRI before treatment were included in this study, and their imaging findings were retrospectively evaluated. RESULTS: Focal splenic lesions were observed in nine patients; these lesions were observed frequently in GLA (n = 5; 50%) or KLA (n = 3; 60%) compared with GSD (n = 1; 13%); however, no significant differences were found between the three groups (P = 0.190). On CT images among eight patients (4 with GLA, 3 with KLA, and 1 with GSD) with focal splenic lesions who underwent CT, the number of focal splenic lesions per patient ranged from 2 to 189 (mean, 42) and the maximum diameter of focal splenic lesions ranged from 2 to 39 mm (mean, 8 mm), while more than 30 focal splenic lesions per patient were observed in 2 (50%) GLA and focal splenic lesions with maximum diameters of ≥10 mm were observed in 4 (100%) GLA but not in KLA or GSD. Ascites was observed in five patients; significant differences were observed among KLA (n = 4; 80%), GLA (n = 1; 10%), and GSD (n = 0; 0%) (P < 0.01). Ascites was significantly more frequent in KLA than in GSD (P < 0.05). CONCLUSION: More than 30 focal splenic lesions per patient and/or focal splenic lesions with maximum diameters of ≥10 mm were observed only in GLA. Focal splenic lesions tended to be less frequent in GSD, whereas ascites tended to be frequent in KLA.

Fatal case of TAFRO syndrome with unilateral adrenal hemorrhage in early-stage disease.

Thrombocytopenia, anasarca, fever, reticulin fibrosis/renal failure, and organomegaly comprise TAFRO syndrome, which was proposed as a distinct clinical entity from iMCD without TAFRO syndrome (iMCD-NOS) due to its aggressive clinical course, refractoriness to corticosteroids, presence of thrombocytopenia, increased level of alkaline phosphatase, and normal level of gammaglobulin. However, diagnosing TAFRO syndrome in its early stages is challenging because it is rare and its diagnostic criteria are complicated. We describe a patient with TAFRO syndrome and adrenal hemorrhage who demonstrated a rapid decline in her clinical condition and did not respond to steroid pulse therapy, resulting in a fatal outcome. In the early stage of her clinical course, she developed unilateral adrenal hemorrhage with mild thrombocytopenia and normal clotting times, suggesting adrenal hemorrhage as a unique manifestation of TAFRO syndrome. In general, patients with TAFRO syndrome exhibit a more aggressive clinical course and poorer outcome than those with iMCD-NOS. To ameliorate this poor prognosis, it is important to diagnose the disease early and immediately start powerful immunosuppressive agents such as tocilizumab. Based on this case, adrenal hemorrhage may suggest TAFRO syndrome, and facilitate the rapid diagnosis of this complicated and rare disease.

Reduction of cycles of bendamustine plus rituximab therapy in the cases with good response for indolent B-cell lymphomas.

Bendamusutine plus rituximab (BR) regimen is one of the standard regimens for indolent B-cell lymphomas, yet the possibility of reduction of cycles of BR therapy without compromising therapeutic effects is not still uncovered. We retrospectively surveyed 57 cases including 40 follicular lymphoma cases who underwent BR regimen in our institute. The overall response (OR) rate and complete response (CR) rate were 86.0% (95% confidential interval (CI), 74.2-93.7) and 54.4% (40.7-67.6), respectively. Five-year overall survival (OS) and 5-years progression-free survival (PFS) were 76.8% and 45.7%, respectively. We then grouped the patients by the number of administered cycles of BR regimen. PFS was significantly longer in 41 cases of the later cessation group (cycle 4-6) than in 16 cases of the earlier cessation group (cycle 1-3) (p = 0.012, 5-years PFS; 46.8% vs. 35.2%, respectively), and both of OR and CR rate of the former was better than the latter (OR rate; 95.1% vs. 62.5%, p < 0.01, CR rate; 61.4% vs. 31.3%, p = 0.04). Interestingly PFS of twenty-one (36.8%) cases receiving just 4 cycles was longer than that of 20 cases who received five or 6 cycles (p < 0.01, 5-years PFS; 71.8% vs. 23.2%, respectively). Focusing on the group of four cycles, the 12 case with CR revealed longer PFS than seven cases with partial response (PR), and median PFS was not reached in CR cases and 16.9 months in the PR cases (p < 0.01). These results suggest that four cycles at least should be administered if possible, and the outcome of the patients who discontinued BR after four cycles was not inferior to that of the cases who received five or six cycles. In conclusion, discontinuation after four cycles may be permissible in some cases with complete response to BR regimen.

Androgen regulation of pulmonary AR, TMPRSS2 and ACE2 with implications for sex-discordant COVID-19 outcomes.

The sex discordance in COVID-19 outcomes has been widely recognized, with males generally faring worse than females and a potential link to sex steroids. A plausible mechanism is androgen-induced expression of TMPRSS2 and/or ACE2 in pulmonary tissues that may increase susceptibility or severity in males. This hypothesis is the subject of several clinical trials of anti-androgen therapies around the world. Here, we investigated the sex-associated TMPRSS2 and ACE2 expression in human and mouse lungs and interrogated the possibility of pharmacologic modification of their expression with anti-androgens. We found no evidence for increased TMPRSS2 expression in the lungs of males compared to females in humans or mice. Furthermore, in male mice, treatment with the androgen receptor antagonist enzalutamide did not decrease pulmonary TMPRSS2. On the other hand, ACE2 and AR expression was sexually dimorphic and higher in males than females. ACE2 was moderately suppressible with enzalutamide administration. Our work suggests that sex differences in COVID-19 outcomes attributable to viral entry are independent of TMPRSS2. Modest changes in ACE2 could account for some of the sex discordance.

Epidemiology of visceral mycoses in patients with acute leukemia and myelodysplastic syndrome: Analyzing the national autopsy database in Japan.

Visceral mycoses (VM) are a deadly common infection in patients with acute leukemia and myelodysplastic syndrome (MDS). We retrospectively analyzed the data from the centralized "Annual Report of Autopsy Cases in Japan" that archives the national autopsy cases since 1989. Among the total of 175,615 archived autopsy cases, 7183 cases (4.1%) were acute leukemia and MDS patients. While VM was only found in 7756 cases (4.4% in total cases), we found VM had a disproportionally high prevalence among acute leukemia and MDS patients: 1562 VM cases (21.7%) and nearly sixfold higher in prevalence. Aspergillus spp. was the most predominant causative agent (45.0%), and Candida spp. was the second (22.7%) among confirmed single pathogen involved cases. The prevalence of Candida spp. infection decreased about 50% due to the widely use of fluconazole prophylaxis, which may skew toward doubling of the Mucormycetes incidence compared to 30 years ago. Complicated fungal infection (> one pathogen) was 11.0% in acute leukemia and MDS in 2015. It was 14.7 times higher than in other populations. Among 937 patients who received allogeneic hematopoietic cell transplantation (HCT), the prevalence of VM was 28.3% and 23.3% with GVHD. Aspergillus spp. was less prevalent, but Candida spp. was more associated with GVHD. Its prevalence remains stable. Although Aspergillus spp. was the primary causative agent, non-albicans Candida spp. was increasing as a breakthrough infection especially in GVHD cases. Complicated pathogen cases were more common in acute leukemia and MDS.

Screening for dental focal infections in febrile patients with hematologic malignancies who received chemotherapy: a retrospective cohort study.

Source of fever in chemotherapy patients is often unknown. Fever can also be fatal. No observational studies have determined the incidence of dental focal infection (DFI)-associated fever, despite oral cavity being a potential source of infection. We report the incidence of fever after chemotherapy in patients with hematological malignancies and their association with DFIs in 441 patients visiting our institution during a 6-year period. Dental treatments, including tooth extraction, were performed, and their oral and hematological profiles were monitored after chemotherapy. Fever was evident in 87 (38.5%) of 226 patients (≥ 38˚C) after the first cycle of chemotherapy. Sepsis due to DFIs (n = 4; 4.6%) was evaluated. Chemotherapy was delayed due to DFI in one case. Fever after chemotherapy should be differentiated from oral infections. Our study emphasizes the significance of DFI in patients with fever after chemotherapy and can help in improving the prognosis of patients.

Clinical efficacy of haematopoietic stem cell transplantation for adult adrenoleukodystrophy.

Accumulated experience supports the efficacy of allogenic haematopoietic stem cell transplantation in arresting the progression of childhood-onset cerebral form of adrenoleukodystrophy in early stages. For adulthood-onset cerebral form of adrenoleukodystrophy, however, there have been only a few reports on haematopoietic stem cell transplantation and the clinical efficacy and safety of that for adulthood-onset cerebral form of adrenoleukodystrophy remain to be established. To evaluate the clinical efficacy and safety of haematopoietic stem cell transplantation, we conducted haematopoietic stem cell transplantation on 12 patients with adolescent-/adult-onset cerebral form/cerebello-brainstem form of adrenoleukodystrophy in a single-institution-based prospective study. Through careful prospective follow-up of 45 male adrenoleukodystrophy patients, we aimed to enrol patients with adolescent-/adult-onset cerebral form/cerebello-brainstem form of adrenoleukodystrophy at early stages. Indications for haematopoietic stem cell transplantation included cerebral form of adrenoleukodystrophy or cerebello-brainstem form of adrenoleukodystrophy with Loes scores up to 13, the presence of progressively enlarging white matter lesions and/or lesions with gadolinium enhancement on brain MRI. Clinical outcomes of haematopoietic stem cell transplantation were evaluated by the survival rate as well as by serial evaluation of clinical rating scale scores and neurological and MRI findings. Clinical courses of eight patients who did not undergo haematopoietic stem cell transplantation were also evaluated for comparison of the survival rate. All the patients who underwent haematopoietic stem cell transplantation survived to date with a median follow-up period of 28.6 months (4.2-125.3 months) without fatality. Neurological findings attributable to cerebral/cerebellar/brainstem lesions became stable or partially improved in all the patients. Gadolinium-enhanced brain lesions disappeared or became obscure within 3.5 months and the white matter lesions of MRI became stable or small. The median Loes scores before haematopoietic stem cell transplantation and at the last follow-up visit were 6.0 and 5.25, respectively. Of the eight patients who did not undergo haematopoietic stem cell transplantation, six patients died 69.1 months (median period; range 16.0-104.1 months) after the onset of the cerebral/cerebellar/brainstem lesions, confirming that the survival probability was significantly higher in patients with haematopoietic stem cell transplantation compared with that in patients without haematopoietic stem cell transplantation (P = 0.0089). The present study showed that haematopoietic stem cell transplantation was conducted safely and arrested the inflammatory demyelination in all the patients with adolescent-/adult-onset cerebral form/cerebello-brainstem form of adrenoleukodystrophy when haematopoietic stem cell transplantation was conducted in the early stages. Further studies are warranted to optimize the procedures of haematopoietic stem cell transplantation for adolescent-/adult-onset cerebral form/cerebello-brainstem form of adrenoleukodystrophy.