Follicular helper T cells (Tfh) play a crucial role in generating high-affinity antibodies (Abs) and establishing immunological memory. Cytokines, among other functional molecules produced by Tfh, are central to germinal center (GC) reactions. This review focuses on the role of cytokines, including IL-21 and IL-4, in regulating B cell responses within the GC, such as differentiation, affinity maturation, and plasma cell development. Additionally, this review explores the impact of other cytokines like CXCL13, IL-10, IL-9, and IL-2 on GC responses and their potential involvement in autoimmune diseases, allergies, and cancer. This review highlights contributions of Tfh-derived cytokines to both protective immunity and immunopathology across a spectrum of diseases. A deeper understanding of Tfh cytokine biology holds promise for insights into biomedical conditions.

Traditionally, diagnostic pathology uses histology representing structural alterations in a disease’s cells and tissues. In many cases, however, it is supplemented by other morphology-based methods such as immunohistochemistry and fluorescent in situ hybridization. Single-cell RNA sequencing (scRNA-seq) is one of the strategies that may help tackle the heterogeneous cells in a disease, but it does not usually provide histologic information. Spatial sequencing is designed to assign cell types, subtypes, or states according to the mRNA expression on a histological section by RNA sequencing. It can provide mRNA expressions not only of diseased cells, such as cancer cells but also of stromal cells, such as immune cells, fibroblasts, and vascular cells. In this review, we studied current methods of spatial transcriptome sequencing based on their technical backgrounds, tissue preparation, and analytic procedures. With the pathology examples, useful recommendations for pathologists who are just getting started to use spatial sequencing analysis in research are provided here. In addition, leveraging spatial sequencing by integration with scRNA-seq is reviewed. With the advantages of simultaneous histologic and single-cell information, spatial sequencing may give a molecular basis for pathological diagnosis, improve our understanding of diseases, and have potential clinical applications in prognostics and diagnostic pathology.

Angiosarcoma associated with lymphedema is a rare soft tissue malignancy that occurs owing to chronic lymphedema, primarily following breast cancer surgery. We present a case of an 83-year-old female who developed angiosarcoma 14 years after undergoing breast cancer surgery. Diagnosis was confirmed through excisional biopsy, histopathological evaluation, and imaging. Computed tomography and magnetic resonance imaging revealed diffuse dermal thickening with an enhanced subcutaneous nodular lesion on the right arm. This unusual case emphasizes the importance of vigilant monitoring in patients with chronic lymphedema post-breast cancer surgery, as early radiologic and clinical detection can facilitate timely intervention and improve outcomes.

Angiosarcoma associated with lymphedema is a rare soft tissue malignancy that occurs owing to chronic lymphedema, primarily following breast cancer surgery. We present a case of an 83-year-old female who developed angiosarcoma 14 years after undergoing breast cancer surgery. Diagnosis was confirmed through excisional biopsy, histopathological evaluation, and imaging. Computed tomography and magnetic resonance imaging revealed diffuse dermal thickening with an enhanced subcutaneous nodular lesion on the right arm. This unusual case emphasizes the importance of vigilant monitoring in patients with chronic lymphedema post-breast cancer surgery, as early radiologic and clinical detection can facilitate timely intervention and improve outcomes.

Angiosarcoma associated with lymphedema is a rare soft tissue malignancy that occurs owing to chronic lymphedema, primarily following breast cancer surgery. We present a case of an 83-year-old female who developed angiosarcoma 14 years after undergoing breast cancer surgery. Diagnosis was confirmed through excisional biopsy, histopathological evaluation, and imaging. Computed tomography and magnetic resonance imaging revealed diffuse dermal thickening with an enhanced subcutaneous nodular lesion on the right arm. This unusual case emphasizes the importance of vigilant monitoring in patients with chronic lymphedema post-breast cancer surgery, as early radiologic and clinical detection can facilitate timely intervention and improve outcomes.

BACKGROUND/AIMS: To compare the efficacy and safety of prucalopride, a novel selective high-affinity 5-hydroxytryptamine type 4 receptor agonist, versus placebo, in Asian and non-Asian women with chronic constipation (CC). METHODS: Data of patients with CC, receiving once-daily prucalopride 2-mg or placebo for 12-weeks, were pooled from 4 double-blind, randomized, phase-III trials (NCT00488137, NCT00483886, NCT00485940 and NCT01116206). The efficacy endpoints were: average of > or = 3 spontaneous complete bowel movements (SCBMs)/week; average increases of > or = 1 SCBMs/week; and change from baseline in each CC-associated symptom scores (bloating, abdominal pain, hard stool and straining). RESULTS: Overall, 1,596 women (Asian [26.6%], non-Asian [73.4%]) were included in this analysis. Significantly more patients in the prucalopride group versus placebo experienced an average of > or = 3 SCBMs/week in Asian (34% vs. 11%, P < 0.001) and non-Asian (24.6% vs. 10.6%, P < 0.001) subgroups. The number of patients reporting an increase of > or = 1 SCBMs/week from baseline was significantly higher in the prucalopride group versus placebo among both Asian (57.4% vs. 28.3%, P < 0.001) and non-Asian (45.3% vs. 24.0%, P < 0.001) subgroups. The difference between the subgroups was not statistically significant. Prucalopride significantly reduced the symptom scores for bloating, hard stool, and straining in both subgroups. CONCLUSIONS: Prucalopride 2-mg once-daily treatment over 12-weeks was more efficacious than placebo in promoting SCBMs and improvement of CC-associated symptoms in Asian and non-Asian women, and was found to be safe and well-tolerated. There were numeric differences between Asian and non-Asian patients on efficacy and treatment emergent adverse events, which may be partially due to the overlap with functional gastrointestinal disorders in non-Asian patients.
Abdominal Pain ; Asian Continental Ancestry Group* ; Constipation* ; Female ; Gastrointestinal Diseases ; Humans ; Serotonin ; Serotonin 5-HT4 Receptor Agonists

BACKGROUND/AIMS: This integrated analysis aimed to identify the factors associated with the most frequently reported treatment-emergent adverse events (TEAEs) in Asian and non-Asian patients with chronic constipation (CC) who receive prucalopride or placebo over 12 weeks. METHODS: Pooled data from four randomized, double-blind, placebo-controlled, multicenter, phase III studies (NCT00488137, NCT00483886, NCT00485940, and NCT01116206) on patients treated with prucalopride 2 mg or placebo were analyzed. The associations between predictors and TEAEs were evaluated based on a logistic regression model. RESULTS: Overall, 1,821 patients (Asian, 26.1%; non-Asian, 73.9%) were analyzed. Prucalopride treatment was significantly associated with diarrhea, headache, and nausea (p<0.001), but not with abdominal pain, compared with placebo. Differences in the prevalence of TEAEs between prucalopride and placebo decreased greatly after the first day of treatment. Compared with non-Asians, Asians were more likely to experience diarrhea and less likely to develop abdominal pain, headache, and nausea. Prior laxative use, CC duration, and body weight were not predictive of any of these TEAEs. CONCLUSIONS: Prucalopride treatment was positively associated with diarrhea, headache, and nausea. Asian patients tended to have a higher frequency of diarrhea but lower frequencies of headache, abdominal pain, and nausea compared with non-Asians.
Abdominal Pain/*chemically induced ; Adult ; Aged ; Aged, 80 and over ; Asian Continental Ancestry Group/statistics & numerical data ; Benzofurans/*adverse effects ; Clinical Trials, Phase III as Topic ; Constipation/*drug therapy/ethnology ; Diarrhea/*chemically induced ; Double-Blind Method ; Female ; Headache/*chemically induced ; Humans ; Male ; Middle Aged ; Multicenter Studies as Topic ; Nausea/chemically induced ; Randomized Controlled Trials as Topic ; Regression Analysis

BACKGROUND/AIMS: This integrated analysis aimed to identify the factors associated with the most frequently reported treatment-emergent adverse events (TEAEs) in Asian and non-Asian patients with chronic constipation (CC) who receive prucalopride or placebo over 12 weeks. METHODS: Pooled data from four randomized, double-blind, placebo-controlled, multicenter, phase III studies (NCT00488137, NCT00483886, NCT00485940, and NCT01116206) on patients treated with prucalopride 2 mg or placebo were analyzed. The associations between predictors and TEAEs were evaluated based on a logistic regression model. RESULTS: Overall, 1,821 patients (Asian, 26.1%; non-Asian, 73.9%) were analyzed. Prucalopride treatment was significantly associated with diarrhea, headache, and nausea (p<0.001), but not with abdominal pain, compared with placebo. Differences in the prevalence of TEAEs between prucalopride and placebo decreased greatly after the first day of treatment. Compared with non-Asians, Asians were more likely to experience diarrhea and less likely to develop abdominal pain, headache, and nausea. Prior laxative use, CC duration, and body weight were not predictive of any of these TEAEs. CONCLUSIONS: Prucalopride treatment was positively associated with diarrhea, headache, and nausea. Asian patients tended to have a higher frequency of diarrhea but lower frequencies of headache, abdominal pain, and nausea compared with non-Asians.
Abdominal Pain/*chemically induced ; Adult ; Aged ; Aged, 80 and over ; Asian Continental Ancestry Group/statistics & numerical data ; Benzofurans/*adverse effects ; Clinical Trials, Phase III as Topic ; Constipation/*drug therapy/ethnology ; Diarrhea/*chemically induced ; Double-Blind Method ; Female ; Headache/*chemically induced ; Humans ; Male ; Middle Aged ; Multicenter Studies as Topic ; Nausea/chemically induced ; Randomized Controlled Trials as Topic ; Regression Analysis

The higher incidence of Streptococcus agalactiae infection in the newborns and pregnant women had been well recognized. The incidence of invasive S. agalactiae infection was recently increasing in both elderly adults and those with comorbid conditions such as diabetes mellitus, liver cirrhosis, malignancy, and abnormalities in immune responses. We report our experience with two diabetic middle-aged men who suffered from S.agalactiae infective endocarditis. Case 1) A 58-year-old man with diabetes mellitus and chronic alcoholism presented with fever and both lower legs weakness. An echocardiography showed two vegetations on the mitral valve. S. agalactiae was identified from blood cultures. He was treated with penicillin G and gentamicin, and he underwent mitral valve replacement surgery because of persistent fever and newly developed brain infarcts. One month later, an amputation of the left lower leg was performed for the embolic gangrene of left lower leg. Case 2) A 57-year-old diabetic man was admitted to our hospital because of fever and left shoulder pain. He had received the incision and drainage to treat left shoulder joint septic arthritis, but he had a continuous fever. On 5th day of admission, culture of pus from the left shoulder joint revealed S. agalactiae. An echocardiography showed a vegetation on the posterior mitral leaflet. He was treated with penicillin G and gentamicin. On 18th day of admission, a mitral valve replacement surgery was performed. He was discharged without recurrence.
Adult ; Aged ; Alcoholism ; Amputation ; Arthritis, Infectious ; Brain* ; Diabetes Mellitus ; Drainage ; Echocardiography ; Endocarditis* ; Female ; Fever ; Gangrene ; Gentamicins ; Humans ; Incidence ; Infant, Newborn ; Intracranial Embolism ; Leg ; Liver Cirrhosis ; Male ; Middle Aged ; Mitral Valve ; Penicillin G ; Pregnant Women ; Recurrence ; Shoulder Joint ; Shoulder Pain ; Streptococcus agalactiae* ; Streptococcus* ; Suppuration

The higher incidence of Streptococcus agalactiae infection in the newborns and pregnant women had been well recognized. The incidence of invasive S. agalactiae infection was recently increasing in both elderly adults and those with comorbid conditions such as diabetes mellitus, liver cirrhosis, malignancy, and abnormalities in immune responses. We report our experience with two diabetic middle-aged men who suffered from S.agalactiae infective endocarditis. Case 1) A 58-year-old man with diabetes mellitus and chronic alcoholism presented with fever and both lower legs weakness. An echocardiography showed two vegetations on the mitral valve. S. agalactiae was identified from blood cultures. He was treated with penicillin G and gentamicin, and he underwent mitral valve replacement surgery because of persistent fever and newly developed brain infarcts. One month later, an amputation of the left lower leg was performed for the embolic gangrene of left lower leg. Case 2) A 57-year-old diabetic man was admitted to our hospital because of fever and left shoulder pain. He had received the incision and drainage to treat left shoulder joint septic arthritis, but he had a continuous fever. On 5th day of admission, culture of pus from the left shoulder joint revealed S. agalactiae. An echocardiography showed a vegetation on the posterior mitral leaflet. He was treated with penicillin G and gentamicin. On 18th day of admission, a mitral valve replacement surgery was performed. He was discharged without recurrence.
Adult ; Aged ; Alcoholism ; Amputation ; Arthritis, Infectious ; Brain* ; Diabetes Mellitus ; Drainage ; Echocardiography ; Endocarditis* ; Female ; Fever ; Gangrene ; Gentamicins ; Humans ; Incidence ; Infant, Newborn ; Intracranial Embolism ; Leg ; Liver Cirrhosis ; Male ; Middle Aged ; Mitral Valve ; Penicillin G ; Pregnant Women ; Recurrence ; Shoulder Joint ; Shoulder Pain ; Streptococcus agalactiae* ; Streptococcus* ; Suppuration