Impact of Diagnosis and Treatment of Chronic Endometritis on Outcomes Before Starting Assisted Reproductive Technology: A Retrospective Study.

This study aimed to investigate the effect of diagnosis and treatment of chronic endometritis (CE) on the outcome of assisted reproductive technology (ART) with or without repeated implantation failure (RIF). This retrospective analysis included patients who underwent pathological examination for diagnosis of CE at Yamagata University Hospital. The examination was performed for all patients planned for ART with or without RIF. Patients who were examined within 6 months of the first oocyte retrieval or embryo transfer were included. We counted the number of CD138-positive cells within the endometrial stroma in patients' specimens and analyzed the patients' clinical information. Clinical rates of pregnancy and implantation were determined. A total of 80 women met the inclusion criteria: 13 CE-negative patients (17.3%) and 67 CE-positive patients (83.7%). A significant decrease was noted in the CD138-positive cell count between the first biopsy and second biopsy after CE treatment (p < 0.001). In addition, no significant differences were noted in ongoing pregnancy rates between the CE-negative patients and those who underwent CE treatment. The CD138-positive cell counts at first biopsy tended to be lower in each pregnancy group than in the non-pregnancy group. For patients planned to undergo ART, examination for diagnosis of CE with or without RIF could be considered. Pathological CD138-positive cell counts were considered useful for CE diagnosis and treatment decision-making. The study findings suggest the efficacy of antimicrobial agents in CE treatment, contributing to improved pregnancy outcomes.

Unplanned hemodialysis initiation: A retrospective analysis of patient characteristics and prognosis in an emergency hospital.

INTRODUCTION: Functional decline occurs during dialysis initiation, particularly in unplanned cases. To prevent unplanned hemodialysis, we aimed to identify associated factors from the first referral to the nephrology department to hemodialysis initiation and assess patient prognosis post-unplanned hemodialysis initiation. METHODS: This retrospective study involved 257 Japanese patients initiating hemodialysis and compared patient characteristics based on whether hemodialysis was planned or unplanned at a single center. Patient outcomes were evaluated in collaboration with maintenance hemodialysis centers. RESULTS: Unplanned hemodialysis initiation correlated with heart failure history (p < 0.05) and infections like pneumonia (p < 0.001). Patients with unplanned hemodialysis initiation had a worse prognosis than those with planned initiation (p < 0.001), and multivariable Cox regression showed it as an independent risk factor for death (p < 0.05). CONCLUSIONS: Hygiene and careful attention to heart failure may reduce unplanned hemodialysis and improve patient well-being and healthcare efficiency. This retrospective analysis highlights crucial considerations for optimizing the initiation of hemodialysis.

Laparoscopic totally extraperitoneal repair for recurrent inguinal bladder hernia: A case report.

We present a case of a recurrent inguinal bladder hernia that was previously unsuccessfully operated on three times and was repaired using totally extraperitoneal repair (TEP). A 79-year-old man presented with a right inguinal swelling that had been treated three times on the same side with anterior approaches. Computed tomography confirmed a recurrent inguinal bladder hernia. TEP was performed after identifying the bladder hernia preoperatively, with previous surgeries that used a plug-and-patch technique through an anterior approach. The extraperitoneal approach allowed the bladder to be reduced without injury and the hernia to be safely repaired using a 3D Max® Light Mesh. The postoperative recovery was uneventful, with no recurrence after 1 year. TEP facilitates the diagnosis and repair of bladder hernias, emphasizing the importance of preoperative diagnosis and the efficacy of endoscopic procedures in bladder hernia repair, even in recurrent cases.

Postoperative early weight-bearing using double plating for periprosthetic, interprosthetic, and interimplant distal femur fractures following total knee arthroplasty: A report of three cases.

Background: Distal femur fractures (DFFs) following total knee arthroplasty (TKA) in older patients often require prolonged non-weight-bearing, thereby decreasing their activities of daily living (ADL) and increasing mortality. This report clarifies early weight-bearing safety and utility by using double-plate fixation on medial and lateral sides (LM180 double-plate fixation) for DFFs following TKA. Case presentation: Three cases of Su Type III periprosthetic, interprosthetic, and interimplant DFFs following TKA, where bone stock was limited, were treated with LM180 double-plate fixation using locking plates through medial and lateral incisions on the distal femur. In interprosthetic and interimplant DFF cases, the proximal section was secured by overlapping the lateral plate +/- medial plate with the proximal femur stem of the intramedullary nail by using monocortical screws and cerclage wires. Early postoperative partial weight-bearing was recommended, and full weight-bearing was allowed 4-5 weeks postoperation. All cases regained independent walking without hardware failure. Average ADL scores, namely, Barthel index (BI) and functional independence measure (FIM), were recovered to 85/100 and 114.7/126, respectively, approaching near-normal values. Conclusion: LM180 double-plate fixation for DFFs such as Su Type III periprosthetic, Vancouver type C interprosthetic, and interimplant DFFs following TKA with limited bone stock can be used to achieve early weight-bearing without fixation failure and help maintain ADL.

Method for quantifying free hemoglobin, distinct from the hemoglobin-haptoglobin complex, in human serum.

The measurement of free hemoglobin (free Hb) in blood is crucial for assessing the risk of organ damage in patients with hemolytic diseases. However, the colorimetric method, commonly used in clinical practice, does not distinguish between free Hb and the hemoglobin-haptoglobin complex (Hb-Hp) in the blood, instead reflecting the total Hb level. Although size-exclusion high-performance liquid chromatography (SEC-HPLC) can specifically measure free Hb, its clinical use is limited by long assay times. Here, we developed a novel assay method for the rapid quantification of free Hb in serum, distinguishing it from Hb-Hp, using a latex agglutination immunoturbidimetric assay (LATIA). This method could be used to measure free Hb in sera in the range of 1 to 100 µg /mL in approximately 15 min using an automatic biochemistry analyzer. Using Hb-spiked serum samples from healthy adults, there was a high correlation with Hb levels determined using the newly developed method and SEC-HPLC, indicating a high specificity for free Hb. This novel assay can be used to monitor levels of free Hb in patients with various hemolytic diseases and to design therapeutic strategies based on measured values. However, further studies are required to assess its clinical performance.

Paternal involvement in childcare and housework and mothers' spanking behavior: The Japanese longitudinal survey of newborns in the 21st century.

BACKGROUND: No previous study reported an association between paternal involvement in childcare and housework and maternal physical punishment. METHODS: Using data from the Japanese Longitudinal Survey of Newborns in the 21st century (N = 38,554), we analyzed responses about fathers' involvement in childcare and housework at 6 months and mothers' spanking of children at 3.5 years. Fathers' involvement in childcare and housework was scored and categorized into quartiles. Spanking frequency was asked in the "often", "sometimes", or "not at all" categories. Multivariable-adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for the mothers' often spanking children were computed for the fathers' involvement in childcare and housework. We also stratified the association by fathers' working hours (40-49, 50-59, or ≥ 60 hours/week). RESULTS: Among the 16,373 respondents, the proportion of mothers who often spanked their children was 4.8%. Compared with the lowest quartile, a higher frequency of paternal involvement in housework was associated with a lower risk of spanking children (p trend = 0.001). Adjustment for covariates attenuated the association, but significant association was observed in the 3rd quartile of paternal involvement in housework [OR (95% CI): 0.77 (0.62-0.96)]. When the fathers worked fewer than 50 hours a week, a significant negative association was observed between the fathers' frequency of childcare and the likeliness of the mothers' spanking their children (p trend = 0.02). CONCLUSIONS: The fathers' active involvement in childcare and housework could reduce the mothers' physical punishment for their children.

Proteomic analysis of serum extracellular vesicles reveals Fibulin-3 as a new marker predicting liver-related events in MASLD.

BACKGROUND: There is a need for novel noninvasive markers for metabolic dysfunction-associated steatotic liver disease (MASLD) to stratify patients at high risk for liver-related events including liver cancer and decompensation. In the present study, we used proteomic analysis of proteins in extracellular vesicles (EVs) to identify new biomarkers that change with fibrosis progression and can predict the development of liver-related events. METHODS: We analyzed serum EVs from 50 patients with MASLD assessed for liver fibrosis by biopsy and identified proteins that altered with advanced fibrosis. A further evaluation was conducted on another cohort of 463 patients with MASLD with biopsy. RESULTS: Eight candidate proteins were identified by proteomic analysis of serum EVs. Among them, serum levels of Fibulin-3, Fibulin-1, and Ficolin 1 correlated with their EV levels. In addition, serum Fibulin-3 and serum Fibulin-1 levels changed significantly with advanced fibrosis. Using another cohort with biopsy, we found that the serum Fibulin-3 concentration was significantly greater in those with advanced fibrosis but that the serum Fibulin-1 concentration was not significantly different. Multivariate Cox proportional hazards analysis revealed that a higher Fibrosis-4 (FIB-4) index and higher serum Fibulin-3 concentration were independent risk factors for liver-related events. When the cutoff value for the serum Fibulin-3 concentration was 6.0 µg/mL according to the Youden index of AUROCs, patients with high serum Fibulin-3 significantly more frequently developed liver-related events than did other patients. Validation using another cohort of 226 patients with clinically diagnosed MASLD confirmed that high serum Fibulin-3 levels are associated with a greater frequency of liver-related events. CONCLUSIONS: Serum Fibulin-3 was identified as a biomarker for predicting liver-related events in patients with MASLD.

The medial prefrontal cortex leaves the hippocampus when it prepares for the future.

Our memories help us plan for the future. In some cases, we use memories to repeat the choices that led to preferable outcomes in the past. The success of these memory-guided decisions depends on close interactions between the hippocampus and medial prefrontal cortex. In other cases, we need to use our memories to deduce hidden connections between the present and past situations to decide the best choice of action based on the expected outcome. Our recent study investigated neural underpinnings of such inferential decisions by monitoring neural activity in the medial prefrontal cortex and hippocampus in rats. We identified several neural activity patterns indicating awake memory trace reactivation and restructuring of functional connectivity among multiple neurons. We also found that these patterns occurred concurrently with the ongoing hippocampal activity when rats recalled past events but not when they planned new adaptive actions. Here, we discussed how these computational properties might contribute to success in inferential decision-making and propose a working model on how the medial prefrontal cortex changes its interaction with the hippocampus depending on whether it reflects on the past or looks into the future.

Serum growth differentiation factor 15 is a novel biomarker with high predictive capability for liver cancer occurrence in patients with MASLD regardless of liver fibrosis.

BACKGROUND AND AIMS: Although metabolic dysfunction-associated steatotic liver disease (MASLD) patients with a Fib-4 index >1.3 are recommended for fibrosis evaluation via elastography or biopsy, a more convenient method identifying high-risk populations requiring follow-up is needed. We explored the utility of serum levels of growth differentiation factor-15 (GDF15), a cell stress-responsive cytokine related to metabolic syndrome, for stratifying the risk of clinical events in MASLD patients. METHODS: Serum GDF15 levels were measured in 518 biopsy-performed MASLD patients, 216 MASLD patients for validation, and 361 health checkup recipients with MASLD. RESULTS: In the biopsy-MASLD cohort, multivariate analysis indicated that the serum GDF15 level was a risk factor for liver cancer, independent of the fibrosis stage or Fib-4 index. Using a GDF15 cutoff of 1.75 ng/mL based on the Youden index, high-GDF15 patients, regardless of fibrosis status, had a higher liver cancer incidence rate. While patients with a Fib-4 index <1.3 or low-GDF15 rarely developed liver cancer, high-GDF15 patients with a Fib-4 index >1.3 developed liver cancer and decompensated liver events at significantly higher rates and had poorer prognoses. In the validation cohort, high-GDF15 patients had significantly higher incidences of liver cancer and decompensated liver events and poorer prognoses than low-GDF15 patients, whether limited to high-Fib-4 patients. Among health checkup recipients with MASLD, 23.0% had a Fib-4 index >1.3, 2.7% had a Fib-4 index >1.3 and >1.75 ng/mL GDF15. CONCLUSIONS: Serum GDF15 is a biomarker for liver cancer with high predictive capability and is useful for identifying MASLD patients requiring regular surveillance.

Brain-implantable needle-type CMOS imaging device enables multi-layer dissection of seizure calcium dynamics in the hippocampus.

Current neuronal imaging methods use bulky lenses that either impede animal behavior or prohibit multi-depth imaging. To overcome these limitations, we developed a lightweight lensless biophotonic system for neuronal imaging, enabling compact and simultaneous visualization of multiple brain layers. Our developed "CIS-NAIST" device integrates a micro-CMOS image sensor, thin-film fluorescence filter, micro-LEDs, and a needle-shaped flexible printed circuit. With this device, we monitored neuronal calcium dynamics during seizures across the different layers of the hippocampus. The CIS-NAIST device revealed distinct calcium activity patterns across the CA1, molecular interlayer, and dentate gyrus. Our findings indicated an elevated calcium amplitude activity specifically in the dentate gyrus compared to other layers. Then, leveraging the multi-layer data obtained from the device, we employed machine learning techniques for seizure classification and prediction. Using Long-Short Term Memory and Hidden Markov Models, we successfully classified seizure calcium activity and predicted seizure behavior based on the multi-layer imaging data. Taken together, our device can enable a minimally invasive method of seizure monitoring that can help elucidate the mechanisms of temporal lobe epilepsy. .

Fast and sustainable production of smart nanofiber mats by solution blow spinning for food quality monitoring: Potential of polycaprolactone and agri-food residue-derived anthocyanins.

The shelf life of perishable foods is estimated through expensive and imprecise analyses that do not account for improper storage. Smart packaging, obtained by agile manufacturing of nanofibers functionalized with natural pigments from agri-food residues, presents promising potential for real-time food quality monitoring. This study employed the solution blow spinning (SBS) technique for the rapid production of smart nanofiber mats based on polycaprolactone (PCL), incorporating extracts of agricultural residues rich in anthocyanins from eggplant (EE) or purple cabbage (CE) for monitoring food quality. The addition of EE or CE to the PCL matrix increased the viscosity of the solution and the diameter of the nanofibers from 156 nm to 261-370 nm. The addition of extracts also improved the mechanical and water-related properties of the nanofibers, although it reduced the thermal stability. Attenuated total reflectance Fourier-transform infrared spectroscopy confirmed the incorporation of anthocyanins into PCL nanofibers. Nanofiber mats incorporated with EE or CE exhibited visible color changes (ΔE ≥ 3) in response to buffer solutions (pH between 3 and 10), and ammonia vapor. Smart nanofibers have demonstrated the ability to monitor fish fillet spoilage through visible color changes (ΔE ≥ 3) during storage. Consequently, smart nanofibers produced by the SBS technique, using PCL and anthocyanins from agro-industrial waste, reveal potential as smart packaging materials for food.

Prognostic impact of the number of resected pelvic nodes in endometrial cancer: Japanese Gynecologic Oncology Group Study JGOG2043 post hoc analysis.

OBJECTIVE: This study aimed to determine whether the number of resected pelvic lymph nodes (PLNs) affects the prognosis of endometrial cancer (EC) patients at post-operative risk of recurrence. METHODS: JGOG2043 was a randomized controlled trial to assess the efficacy of three chemotherapeutic regimens as adjuvant therapy in EC patients with post-operative recurrent risk. A retrospective analysis was conducted on 250 patients who underwent pelvic lymphadenectomy alone in JGOG2043. The number of resected and positive nodes and other clinicopathologic risk factors for survival were retrieved. RESULTS: There were 83 patients in the group with less than 20 PLNs removed (group A), while 167 patients had 20 or more PLNs removed (group B). There was no significant difference in patients' backgrounds between the two groups, and the rate of lymph node metastasis was not significantly different. There was a trend toward fewer pelvic recurrences in group B compared with group A (3.5% vs. 9.6%; p=0.050). Although Kaplan-Meier analysis showed no statistically significant difference in survival rates between the two groups (5-year overall survival [OS]=90.3% vs. 84.3%; p=0.199), multivariate analysis revealed that resection of 20 or more nodes is one of the independent prognostic factors (hazard ratio=0.49; 95% confidence interval=0.24-0.99; p=0.048), as well as surgical stage, high-risk histology, and advanced age for OS. CONCLUSION: Resection of 20 or more PLNs was associated with improved pelvic control and better survival outcomes in EC patients at risk of recurrence who underwent pelvic lymphadenectomy alone and were treated with adjuvant chemotherapy.

High incidence of lung cancer death after curative endoscopic submucosal dissection for superficial esophageal squamous cell carcinoma.

BACKGROUND AND AIM: Following treatment of superficial esophageal squamous cell carcinoma (ESCC), surveillance for a second primary malignancy (SPM) is necessary. However, detailed evidence regarding the timing and prognosis of SPMs is insufficient. We aimed to clarify the details of SPMs and their effects on patient outcomes. METHODS: This retrospective, multicenter study involved 11 hospitals. Patients with superficial ESCC curatively resected using endoscopic submucosal dissection between May 2005 and December 2012, were included in this study. RESULTS: The 5-year survival rate of 187 patients was 92.6% during a median follow-up duration of 96.8 months. Thirty-one patients died, 14 of whom died of SPMs. Compared to patients with SPMs detectable by esophagogastroduodenoscopy (EGD), patients with SPMs detectable only by modalities other than EGD had a significantly higher mortality rate (p < 0.001). Patients with second primary lung cancer (LC) had a high mortality rate (56.3%). Univariate and multivariate analyses showed that multiple Lugol-voiding lesions (LVLs) tended to be associated with SPMs (p = 0.077, hazard ratio [HR] 4.43, 95% confidence interval [CI]: 0.91-6.50), and metachronous ESCC was an independent risk factor for the incidence of second primary LC (p = 0.037, HR 3.51, 95% CI: 1.08-11.41). CONCLUSIONS: SPMs that cannot be detected by EGD, such as LC, must be considered after the curative resection of ESCC. We suggest strict screening by both EGD and computed tomography for patients with multiple LVLs or metachronous ESCC to detect SPMs in their early stages.

Endoscopic Features of Synchronous Multiple Early Gastric Cancers: Findings from a Nationwide Cohort.

INTRODUCTION: We investigated the factors associated with synchronous multiple early gastric cancers and determined their localization. METHODS: We analyzed 8,191 patients who underwent endoscopic submucosal dissection for early gastric cancers at 33 hospitals in Japan from November 2013 to October 2016. Background factors were compared between single-lesion (n = 7,221) and synchronous multi-lesion cases (n = 970) using univariate and multivariate analyses. We extracted cases with two synchronous lesions (n = 832) and evaluated their localization. RESULTS: Significant independent risk factors for synchronous multiple early gastric cancer were older age (≥75 years old) (odds ratio [OR] = 1.257), male sex (OR = 1.385), severe mucosal atrophy (OR = 1.400), tumor localization in the middle (OR = 1.362) or lower region (OR = 1.404), and submucosal invasion (OR = 1.528 [SM1], 1.488 [SM2]). Depressed macroscopic type (OR = 0.679) and pure undifferentiated histology OR = 0.334) were more common in single early gastric cancers. When one lesion was in the upper region, the other was more frequently located in the lesser curvature of the middle region. When one lesion was in the middle region, the other was more frequently located in the middle region or the lesser curvature of the lower region. When one lesion was in the lower region, the other was more frequently located in the lesser curvature of the middle region or the lower region. CONCLUSION: Factors associated with synchronous multiple early gastric cancer included older age, male sex, severe mucosal atrophy, tumor localization in the middle or lower region, and tumor submucosal invasion. Our findings provide useful information regarding specific areas that should be examined carefully when one lesion is detected.

A novel artificial intelligence-based endoscopic ultrasonography diagnostic system for diagnosing the invasion depth of early gastric cancer.

BACKGROUND: We developed an artificial intelligence (AI)-based endoscopic ultrasonography (EUS) system for diagnosing the invasion depth of early gastric cancer (EGC), and we evaluated the performance of this system. METHODS: A total of 8280 EUS images from 559 EGC cases were collected from 11 institutions. Within this dataset, 3451 images (285 cases) from one institution were used as a development dataset. The AI model consisted of segmentation and classification steps, followed by the CycleGAN method to bridge differences in EUS images captured by different equipment. AI model performance was evaluated using an internal validation dataset collected from the same institution as the development dataset (1726 images, 135 cases). External validation was conducted using images collected from the other 10 institutions (3103 images, 139 cases). RESULTS: The area under the curve (AUC) of the AI model in the internal validation dataset was 0.870 (95% CI: 0.796-0.944). Regarding diagnostic performance, the accuracy/sensitivity/specificity values of the AI model, experts (n = 6), and nonexperts (n = 8) were 82.2/63.4/90.4%, 81.9/66.3/88.7%, and 68.3/60.9/71.5%, respectively. The AUC of the AI model in the external validation dataset was 0.815 (95% CI: 0.743-0.886). The accuracy/sensitivity/specificity values of the AI model (74.1/73.1/75.0%) and the real-time diagnoses of experts (75.5/79.1/72.2%) in the external validation dataset were comparable. CONCLUSIONS: Our AI model demonstrated a diagnostic performance equivalent to that of experts.

Pre-pregnancy body mass index and low birthweight: Secondary data analysis using health insurance claims data in Japan.

AIM: For women, being underweight increases their susceptibility to osteoporosis, anemia, and other conditions and affects the weight of their infants and the well-being of future generations. This study examined the association between low pre-pregnancy body mass index (BMI) and low birthweight using health insurance claims data and health checkup data, including weight measurements. METHODS: We used health insurance claims data and health checkup data (JMDC, Tokyo, Japan) of women and their newborns in Japan between 2006 and 2020. We used checkup data, which included more accurate weight measurements and blood test-based diagnoses of anemia and hyperlipidemia compared to self-reported data. Maternal pre-pregnancy BMI was compared across three groups: underweight (BMI <18.5 kg/m2), normal weight (BMI 18.5-24.9 kg/m2), and overweight (BMI ≥25.0 kg/m2). The primary outcome was low birthweight (<2500 g), and secondary outcome was preterm childbirth. Logistic regression analyses were conducted to compare outcomes in the three groups by BMI. The underweight BMI group was considered as the reference group. A subgroup analysis was performed by maternal age. RESULTS: In total, 16 363 mothers (underweight, 3418 [21%], normal weight, 11 493 [70%], and overweight, 1452 [8.9%]) were included. The risk of primary outcome (low birthweight) was significantly lower in the normal weight group than in the underweight group (4.6% vs. 5.7%; adjusted odds ratio 0.78 [95% confidence interval: 0.65-0.96]). In the subgroup analyses, no significant differences were noted in the incidences of low birthweight and preterm childbirth between maternal age groups. CONCLUSIONS: Pre-pregnancy BMI was associated with an increased risk of delivering low-birthweight infant. Awareness about the importance of women's pre-pregnancy health and appropriate BMI may reduce the incidence of low birthweight.

A machine learning model for predicting the lymph node metastasis of early gastric cancer not meeting the endoscopic curability criteria.

BACKGROUND: We developed a machine learning (ML) model to predict the risk of lymph node metastasis (LNM) in patients with early gastric cancer (EGC) who did not meet the existing Japanese endoscopic curability criteria and compared its performance with that of the most common clinical risk scoring system, the eCura system. METHODS: We used data from 4,042 consecutive patients with EGC from 21 institutions who underwent endoscopic submucosal dissection (ESD) and/or surgery between 2010 and 2021. All resected EGCs were histologically confirmed not to satisfy the current Japanese endoscopic curability criteria. Of all patients, 3,506 constituted the training cohort to develop the neural network-based ML model, and 536 constituted the validation cohort. The performance of our ML model, as measured by the area under the receiver operating characteristic curve (AUC), was compared with that of the eCura system in the validation cohort. RESULTS: LNM rates were 14% (503/3,506) and 7% (39/536) in the training and validation cohorts, respectively. The ML model identified patients with LNM with an AUC of 0.83 (95% confidence interval, 0.76-0.89) in the validation cohort, while the eCura system identified patients with LNM with an AUC of 0.77 (95% confidence interval, 0.70-0.85) (P = 0.006, DeLong's test). CONCLUSIONS: Our ML model performed better than the eCura system for predicting LNM risk in patients with EGC who did not meet the existing Japanese endoscopic curability criteria. We developed a neural network-based machine learning model that predicts the risk of lymph node metastasis in patients with early gastric cancer who did not meet the endoscopic curability criteria.

Advancements in Non-Dopaminergic Treatments for Schizophrenia: A Systematic Review of Pipeline Developments.

INTRODUCTION: Conventional antipsychotic drugs that attenuate dopaminergic neural transmission are ineffective in approximately one-third of patients with schizophrenia. This necessitates the development of non-dopaminergic agents. METHODS: A systematic search was conducted for completed phase II and III trials of compounds for schizophrenia treatment using the US Clinical Trials Registry and the EU Clinical Trials Register. Compounds demonstrating significant superiority over placebo in the primary outcome measure in the latest phase II and III trials were identified. Collateral information on the included compounds was gathered through manual searches in PubMed and press releases. RESULTS: Sixteen compounds were identified; four compounds (ulotaront, xanomeline/trospium chloride, vabicaserin, and roluperidone) were investigated as monotherapy and the remaining 12 (pimavanserin, bitopertin, BI 425809, encenicline, tropisetron, pregnenolone, D-serine, estradiol, tolcapone, valacyclovir, cannabidiol, and rimonabant) were examined as add-on therapy. Compared to the placebo, ulotaront, xanomeline/trospium chloride, vabicaserin, bitopertin, estradiol, cannabidiol, rimonabant, and D-serine showed efficacy for positive symptoms; roluperidone and pimavanserin were effective for negative symptoms; and encenicline, tropisetron, pregnenolone, tolcapone, BI 425809, and valacyclovir improved cognitive function. DISCUSSION: Compounds that function differently from existing antipsychotics may offer novel symptom-specific therapeutic strategies for patients with schizophrenia.