Posttraumatic malunion with combination of angular, rotational, and shortening deformity of the proximal phalanx may cause scissoring of a finger and impairment of hand function. Cosmetic disfigurement and severe dysfunction of fingers require surgical correction, most often via open corrective osteotomies and rigid fixation with a plate or screws. However, such an approach requires a longer incision, inevitably results in a scar, and has a higher potential for extensor tendon adhesion. Also, abruption of the periosteum and plating of the phalange requires longer bone healing time. Thus, we devised a technique of minimally invasive correction of phalangeal malunion using an external mini-fixator. We presented representative three cases of malunited fractures of phalanges treated with the Ilizarov mini-fixator in adolescence and review reports of similar cases. The usage of Ilizarov mini-fixator provided excellent outcomes for posttraumatic malunion of three fingers.

Immune checkpoint inhibitors (ICIs) are widely used for various types of advanced cancers. Currently, three types of ICIs are clinically available, a monoclonal antibody targeting cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), and antibodies targeting the programmed cell death protein-1 (PD-1) and its ligand, programmed cell death ligand 1 (PD-L1). Although ICIs have improved the survival rates of several types of cancers, they induce immune-related adverse events (irAE) by their enhancement of immune responses. The pituitary gland is one of the common targets of irAE. In general, different clinical presentations of autoimmune pituitary dysfunctions are observed between anti-CTLA-4 and anti-PD-1/anti-PD-L1 antibodies, with anti-CTLA-4 inducing hypophysitis with multiple pituitary hormone deficiencies and targeting the PD-1/PD-L1 axis inducing isolated adrenocorticotropic hormone deficiency. This review describes the current understanding of the pathophysiology, clinical manifestation, and management of hypophysitis caused by ICIs.

Neurodegenerative diseases can manifest as psychiatric symptoms in the prodromal phase, before the onset of core symptoms such as neurological, motor, and cognitive symptoms. Positron emission tomography (PET) has made it possible to detect the pathology of some neurodegenerative diseases in vivo. Many studies have indicated that depression is a preclinical symptom of neurodegenerative diseases. Approximately 10% of non-demented participants with depression developed Alzheimer's disease (AD) during the follow-up period. The prevalence of depression/dysphoria was 42.9% in the preclinical stage of dementia with Lewy bodies. Depression was present in 33.3% of patients with preclinical behavioral-variant frontotemporal lobar degeneration. Approximately 10% of patients had a history of depression at the time of diagnosis with Parkinson's disease. PET studies have revealed the pathology of neurodegenerative diseases in some cases of geriatric depression. Increased brain amyloid-beta deposition in late-onset depression is a possible reflection of prodromal AD. The severity of depression was significantly associated with greater inferior temporal tau and marginally associated with greater entorhinal cortex tau, and depression was associated with significantly greater mean cortical tau deposition. Thus, the presence of depression as a preclinical/prodromal symptom of neurodegenerative diseases has been demonstrated by epidemiological, pathological, and biomarker studies. A growing body of evidence from PET studies indicates that some cases of geriatric depression have pathologies of degenerative neurological disease. In the future, it is expected that PET will be utilized as an imaging biomarker for diagnosis of psychiatric disorders and development of new therapeutic agents.

Background: This study was performed to evaluate the orientation of lower esophageal sphincter (LES) pressure in patients with untreated achalasia using three-dimensional high-resolution manometry (3D-HRM). Methods: The study involved 20 patients with untreated achalasia (10 men, 60 [47-74] years of age). The 3D-HRM assembly had 32 standard channels and 12 3D channels. During basal LES pressure measurements, the orientations of the LES high- and low-pressure zones were evaluated at end-expiration. The directional relationships between the orientation of the LES high- and low-pressure zones were also evaluated. Results: The LES high-pressure zones were located on the greater curvature side in nine (45%) patients, from the greater curvature to posterior wall side in six (30%), and from the greater curvature to anterior wall side in five (25%). The LES high-pressure zones were located mainly on the greater curvature side, but there were some variations of the orientation among the patients. The LES low-pressure zones were most frequently located from the lesser curvature to the posterior wall side in 11 (55%) patients, from the lesser curvature to anterior wall side in 6 (30%), on the posterior wall side in 2 (10%), and on the anterior wall side in 1 (5%). Significant differences were found in the directional relationships between the orientation of the LES high- and low-pressure zones (P = 0.0053). Conclusions: This is the first report from Japan focusing on the LES pressure orientation using 3D-HRM. Such evaluation may be useful for clarifying the pathophysiology of achalasia.

Background: In Japan, increasing the number of ambulance requests, the case with the use of respiratory assistance devices in prehospital care by paramedics is also increasing¹. When patient experiences respiratory failure, the first responders frequently select a respiratory assist device (RAD) such as Bag Valve Mask (BVM), Jackson Rees (JR), or BVM with Gas Supply Valve^® (BVM+GSV). This is based on both evaluation and experience as there is no study indicating which RAD is the best choice at the pre-hospital emergency site. This study clarified the precautions when using BVM, JR, and BVM+GSV in pre-hospital emergency medical care with healthy volunteers. Methods: Twenty healthy adults were fitted with a RAD while breathing spontaneously, and changes in vital signs and ETCO₂ were observed. Results: The level of ETCO₂ became elevated after each RAD was attached. The value was significantly higher in the JR group than in the others. Conclusions: The study showed that even in the presence of spontaneous breathing, ETCO₂ increased markedly with the application of respiratory assist devices that are used in pre-hospital care for conditions such as hypoxemia and ventilatory disturbance. The increase in ETCO₂ was particularly significant in the JR group, suggesting the need for caution when selecting JRs for pre-hospital care. As the number of subjects was only 20 for each RAD, studies with a larger sample size are needed.

Background: The emergence of molecularly targeted agents (MTAs) has altered the treatment landscape for hormone receptor-positive (HR+), human epidermal growth factor 2-negative (HER2−) advanced breast cancer (ABC) /metastatic breast cancer (MBC). Multiple guidelines recommend molecularly targeted therapy as first-line treatment for HR+/HER2− ABC/MBC. However, optimal treatment for disease progression during MTA therapy remains undetermined. This study evaluated the suitability of different MTA types for this patient subgroup. Methods: In this retrospective study, we analyzed the electronic health records of 56 patients with HR+/HER2− ABC/MBC receiving treatment with palbociclib, abemaciclib, or everolimus in our center between April 2014 and June 2021. Results: Overall, 39, 14, and 35 regimens using palbociclib, abemaciclib, and everolimus, respectively, were identified. Three and 53 patients were premenopausal and postmenopausal, respectively. MTAs were included in the 1^st-11^th lines of treatment. Time to failure (TTF) was significantly different among the three MTAs. In contrast, TTF did not significantly differ among the 50 regimens that included CDK4/6 inhibitors, with/without prior mTOR inhibitor use, and the 35 regimens that included mTOR inhibitors, with/without prior CDK4/6 inhibitor use. Conclusions: The sequential use of different MTA classes did not affect the TTF of another MTA. mTOR inhibitor + exemestane is a favorable treatment option after CDK4/6 inhibitor + hormone therapy, and CDK4/6 inhibitor + hormone therapy is suitable for patients previously treated with mTOR inhibitor + exemestane. Although this study was retrospective and conducted at a single center, the present findings are useful for treatment selection in clinical practice.

Background: Trauma is a serious medical and economic burden worldwide, and patients with traumatic injuries have a poor survival rate after cardiac arrest. The authors developed a prediction model specific to prehospital trauma care and used machine learning techniques to increase its accuracy. Methods: This retrospective observational study analyzed data from patients with blunt trauma injuries due to traffic accidents and falls from January 1, 2018, to December 31, 2019. The data were collected from the National Emergency Medical Services Information System, which stores emergency medical service activity records nationwide in the United States. A random forest algorithm was used to develop a machine learning model. Results: The prediction model had an area under the curve of 0.95 and a negative predictive value of 0.99. The feature importance of the predictive model was highest for the AVPU (Alert, Verbal, Pain, Unresponsive) scale, followed by oxygen saturation (SpO₂). Among patients who were progressing to cardiac arrest, the cutoff value was 89% for SpO₂ in nonalert patients. Conclusions: The machine learning model was highly accurate in identifying patients who did not develop cardiac arrest.

Background: We previously analyzed data from blood examination screenings, including serum Krebs von den Lungen (KL) -6 level, before starting biologic treatment for psoriasis in a real-world setting. However, we did not follow change in KL-6 level after the initiation of biologics. Furthermore, there has been no follow-up study of certolizumab pegol, risankizumab, or tildrakizumab. This study evaluated change in serum KL-6 levels in patients during treatment with biologics, including certolizumab pegol, risankizumab, and tildrakizumab. Methods: We analyzed data from 111 patients. Change in KL-6 level was regarded as significant if it increased to greater than 500 U/mL at least once and if the maximum level after treatment with biologics was at least 1.5 times that of the baseline level. Results: KL-6 level significantly changed during treatment with TNF inhibitors, IL-17 inhibitors, and IL-23 inhibitors in 9 (20.9%), 2 (6.3%), and 2 (5.6%) patients, respectively. Mean age, mean baseline KL-6 level, and frequency of TNF inhibitor use were higher in patients with a significant change in KL-6 level than those in patients without a significant change. Ten patients had minor interstitial changes on chest CT scans but no clinical signs suggesting interstitial pneumonia. Conclusions: Older patients with psoriasis and high baseline KL-6 levels must be carefully monitored during treatment with biologics, especially TNF inhibitors. Monitoring of KL-6 level and chest CT scans is necessary to exclude the possibility of drug-induced interstitial pneumonia.

Background: The optimal treatment modality for locally advanced prostate cancer has not been established. Radiotherapy, hormonal therapy, and combination treatments are the main strategies, although the feasibility of radical prostatectomy as a first-line therapy needs to be considered. This retrospective analysis of pathological results of extracted specimens evaluated long-term oncological outcomes for high-risk prostate cancer treated surgically. The association of number of risk factors with long-term outcome was specifically analyzed. Methods: We identified patients with high-risk prostate cancer who underwent laparoscopic radical prostatectomy, without neoadjuvant therapy, at Nippon Medical School from 2000 to 2012. Risk factors were a prostate-specific antigen (PSA) concentration ≥20 ng/mL, pathological ≥T3, and pathological Gleason Score ≥8. Biological failure was defined as a PSA concentration ≥0.2 ng/mL. Results: 222 men were identified. One patient had a positive lymph node status, and there was a significant difference in surgical margin positivity (52 men, 68.4% vs 56 men 38.4%) between patients with and without biochemical failure. Among patients meeting the high-risk criteria with a follow-up of up to 133 months, the biochemical recurrence (BCR) -free survival rates at 5 and 10 years were 62.8% and 58.4%, respectively, and mean time to BCR was 14.0 months. BCR-free survival rates at 5 and 10 years were 73.6% and 71.4%, respectively, for 1 risk factor, 48.7% and 34.6% for 2 factors, and 34.5% and 34.5% for 3 factors. Patients with a single risk factor had a significantly better outcome than those with multiple risk factors. The overall survival rates at 5 and 10 years were 94.6% and 93.7%, and the cancer-specific survival rate was 100% at both 5 and 10 years. Conclusions: Reasonable long-term oncological outcomes can be achieved by surgical treatment for high-risk prostate cancer. Patients with 1 risk factor had a significantly better BCR-free rate than those with multiple risk factors.

Background: Down syndrome (DS) is the most frequent chromosomal aberration; however, knowledge of associated health issues in adulthood is inadequate. We analyzed health data from Japanese adults with DS. Methods: We conducted a retrospective chart review of 151 patients with DS who visited the Internal Medicine Outpatient Department of the Tokyo Metropolitan Kita Medical and Rehabilitation Center for the Disabled. Results: Endocrine disorders such as obesity, hyperlipidemia, and hyperuricemia were most common in adulthood (≤40 years) and senescence (>40 years); neurological diseases were more prevalent in senescence. Multimorbidity was noted even patients with DS who were younger than 30 years, and the prevalence increased with age. Only 21 patients (13.9%) with DS visited our hospital with referral letters from pediatricians; 94 patients (62.3%) visited without such referrals from other medical institutions. Patients without a referral letter had a mean of 3.1 comorbidities per patient. Moreover, medical care for some people with DS was interrupted during childhood. Conclusions: Prevention and detection of comorbidities in patients with DS requires continuous medical care from childhood through adulthood. Recently, DS has been diagnosed by chromosome testing and genetic counseling. Clinical geneticists and genetic counselors can help patients with DS, and their caregivers, to obtain appropriate health care and achieve well-being on their own by seamlessly engaging them throughout childhood and adulthood.

Background: Non-invasive cardiovascular assessment has become an alternative to invasive techniques. VaSera^®, a vascular screening device, measures arterial stiffness with the cardio-ankle vascular index (CAVI); it also measures cardiophysiological variables of ejection time (ET) and pre-ejection period (PEP). We aimed to apply the parameters obtained by VaSera^® to estimate heart function based on left ventricular end-systolic elastance/arterial elastance (Ees/Ea) and to assess the minimal required number of measurements for estimation. Methods: We conducted an experimental laboratory study for healthy volunteers. Using the previously established formula, the Ees/Ea value of each participant was estimated using ET and PEP values measured by VaSera^®. The intraclass correlation coefficient (ICC) assessed the minimum required number of measurements. Concordance correlation coefficient (CCC) and Bland and Altman analysis assessed variation of Ees/Ea estimation against the trimmed average. Results: A total of 660 measurements from 132 participants were included. The Ees/Ea estimates from the VaSera^® were 1.5 [1.2, 1.9]. The ICC for Ees/Ea was 0.71 (95% confidence interval: 0.65-0.77), suggesting that four measurements were required. The CCC between the trimmed average of Ees/Ea and the mean of four Ees/Ea estimates was 0.99. Bland and Altman analysis showed excellent agreement for the mean of four Ees/Ea estimates and the trimmed average of Ees/Ea. Conclusions: For screening of heart failure, the Ees/Ea estimated using non-invasive vascular-stiffness assessment device would be tolerable and four sequential measurements were required.

Background: Although coronary artery disease (CAD) is characterized by epicardial atherosclerosis and microvascular disease, the importance of evaluating microvascular dysfunction has not been sufficiently recognized in clinical practice. We estimated microvascular disease severity by assessing hyperemic microvascular resistance (MVR), as determined by absolute quantification of myocardial blood flow (MBF) with ¹³N-ammonia positron emission tomography-myocardial perfusion imaging (PET-MPI). Methods: We retrospectively collected data for 23 CAD patients who underwent both stress/rest PET-MPI and invasive coronary angiography (CAG) with fractional flow reserve (FFR) measurement. Among 30 vessels for which FFR measurement was performed, 13 had a low FFR (FFR ≤0.75). For each patient, myocardial segments of a standard 17-segment model were assigned to the stenotic myocardial area perfused by the FFR-measured vessel and a reference normal-perfusion area based on PET-MPI and the coronary distribution on CAG. Hyperemic MVR was calculated by using the formula, hyperemic MVR = hyperemic mean blood pressure × FFR/hyperemic MBF of the stenotic vessel. Results: A strong negative correlation was observed between hyperemic MVR and hyperemic MBF in the reference normal-perfusion area (R = −0.758, P<0.001). Conclusion: Microvascular disease severity in chronic CAD can be estimated by hyperemic MBF of the normal-perfusion area with ¹³N-ammonia PET-MPI.

Objective: Common peroneal nerve (C-PN) entrapment neuropathy is the most common peripheral nerve neuropathy of the legs. C-PN decompression surgery is less invasive but may result in neurological complications. We report a rare case of nerve paralysis immediately after C-PN decompression surgery. Case Report: An 85-year-old man presented with leg numbness and pain. An electrophysical study revealed C-PN entrapment in the affected area and he underwent surgical decompression. Immediately after the procedure he complained of slight paralysis without pain (manual muscle test: 3/5), which gradually worsened and was complete at 60 min after surgery. We re-opened the skin incision 3 hours after the first operation and found that a subcutaneous suture had been applied to the connective tissue near the C-PN, resulting in marked compression of the nerve. After release of the suture his paralysis improved immediately. We confirmed that there was no other nerve compression and finished the operation. His paralysis disappeared completely. Conclusion: Peripheral nerve surgery, including C-PN decompression surgery, is less invasive, and the risk of complications is low. However, because the C-PN is located in the shallow layer under the skin, an excessively deep suture in the subcutaneous layer may compress the nerve and elicit nerve palsy. Therefore, careful postoperative follow-up is necessary because early decompression leads to good surgical results.

On the basis of postoperative histopathological findings, a 29-year-old nulliparous woman was diagnosed as having ovotesticular disorder of sex development (DSD). She had undergone unilateral gonadectomy at age 6 years and vulvoplasty and vaginoplasty at age 8 years. Her karyotype was 46, XX. She had dyspareunia because of a narrow vagina, but her uterus and left gonad were normal. Spontaneous ovulation was confirmed, but sexual intercourse was impossible because of dyspareunia, despite vaginal self-dilatation with a vaginal dilator. Artificial insemination was initiated; however, five cycles failed to yield a viable pregnancy. We decided to perform in vitro fertilization (IVF), which resulted in conception. During IVF we administered intravenous anesthesia before oocyte collection to reduce her distress due to insufficient lumen expansion after vaginoplasty. The patient delivered a healthy male infant weighing 2,558 g at 37 weeks of gestation via cesarean section, which was performed because of gestational hypertension. This is the eighth report of a viable neonate born from a patient with ovotesticular DSD after gonadectomy and the first such pregnancy achieved by IVF. Therefore, IVF may be an effective option for infertile patients with ovotesticular DSD. Additionally, to prevent dyspareunia, self-management of the plastic vagina is important during the peri- and postoperative periods of early vaginoplasty.