Dry Mouth Research Articles

Regenerative fibroblasts derived from autologous skin tissue for the treatment of Sjögren’s syndrome: a case report

BackgroundSjögren’s syndrome (SS) is a systemic autoimmune disease, with major symptoms including dry mouth and dry eyes, for which there is no effective treatment. Recent studies have demonstrated that mesenchymal stem cells (MSCs) are effective in the treatment of SS, but the efficacy of allogeneic MSCs is affected by variability among different cell donors, and they are easily cleared by the immune system of the recipient. Autologous MSCs are one of the ideal options for the treatment of SS; however, their function decreases with age. Regenerative fibroblast (rFib) is a type of new MSC obtained through chemical reprogramming technology from skin fibroblasts. In this study, we report the safety and efficacy of intravenous infusion of autologous rFib in a volunteer with SS.Case reportIn March 2021, the volunteer was diagnosed with SS due to positive anti-SSB antibodies, lymphocyte infiltration in the lip gland, dry eyes, and a large area of purpura in both lower limbs. From May 2021 to November 2022, she received allogeneic Umbilical cord mesenchymal stem cells (UCMSC) therapy (5.0 × 107 UCMSCs per time, totaling 10 infusions), but her condition did not improve. In May 2023, the rFib for the volunteer was prepared, meeting the quality standard of T/CSCB0003-2021 Human Mesenchymal Stem Cells. Between October 2023 and June 2024, the volunteer received a total of 12 intravenous transfusions of autologous rFib. After the treatments, the volunteer experienced no recurrence of purpura in both lower limbs. Symptoms of dry mouth, dry eyes, and fatigue were relieved. ESR, B lymphocytes, rheumatoid factor IgM, and IgA declined, while the proportion of NK cells increased, and most of the cytokines returned to normal levels. In vitro experiments showed that rFib could significantly inhibit the proliferation of T lymphocytes after PHA stimulation. No adverse effects were associated with the use of rFib in the volunteer during the clinical trial.SummaryThe results of this clinical trial indicate that intravenous injections of autologous rFib are both safe and effective for treating SS. Autologous rFib may be more suitable for treating autoimmune diseases than allogeneic MSCs.

P-29 HONEYMOON IN LATE PREGNANCY

Abstract Introduction During pregnancy there is a partial decrease in the function of immune system which would end with suppression of autoimmune diseases, even type 1 diabetes (T1DM) (1-2). We report a pregnant women with T1DM who was suffering from severe hypoglycemia even with very low insulin dosages in her third trimester. Clinical Case A 27 year old young lady was referred to our clinic with HbA1c level of 12.7%. She had no symptom other than slight nausea and dry mouth. Her β-HCG level was 55 mIU/ml and her plasma glucose level was 435 mg/dl. She was diagnosed with T1DM about one year ago, was started with intensive insulin regimen about 80 IU/day totally, which she did not use ever since. We hospitalized her and started intravenous (IV) hydration and IV insulin, which we switched to subcutaneous insulin. She was educated by our dietitian and by our diabetes-clinic nurse. As the insulin dosages increased, it was detected that she was pregnant. She was offered for therapeutic abortus but did not accept. Her blood glucose measurements improved and she was discharged with morning: 12 IU, afternoon:8 IU, evening:15 IU insulin aspart and night:18 IU insulin detemir dosages. In the follow up, her Hba1c level decreased to 8.7 % in the 2nd month and to 6.7% at the 20th week. Her fasting blood glucose levels were between 87-102 mg/dl and 1st hour postprandial levels were between 110-137 mg/dl. She dropped from the follow up by her own decision. At her 30th pregnancy week, she came with hypoglycemia and she had decreased her insulin dosages to morning: 2 IU, afternoon: 2IU, evening: 3IU insulin aspart and no insulin detemir. Her plasma cortisol level was 18 mcg/dl, alanine aminotransferase (ALT): 12 IU/L, gamma glutamyl transferase (GGT): 28 IU/L, creatinine (Cre):0.8 mg/dl, and Hba1c:5.3%. Her abdominal ultrasonography (USG) was normal. She was diagnosed with honeymoon period in T1DM and was informed about strict blood glucose measurement. Conclusion T1DM would disappear for a long while or regress greatly in some pregnant women even in the late years of their disease (2). Insulin -free period after the pregnancy would last even two and a half years or huge reduction in insulin dosage during pregnany period would even start after 20 years of T1DM (2). In our case, the patient started to use very low insulin dosages at around 30th pregnancy week and after one and half year of her diagnosis of T1DM.

Preparation of sodium hyaluronate coated liposomes: effect of polymer molecular weight, coating concentration, amount of charged lipids and type of hydration medium on the stability

In this study, liposomes consisting of soybean phosphatidyl choline (SoyPC) and different molar concentrations (10 mol% and 20 mol%) of dioleoyl trimethylammoniumpropane (DOTAP) were prepared by the thin film hydration method and coated with sodium hyaluronate (NaHA) of different MWs (8–15 kDa, 30–50 kDa and 90–130 kDa) and concentrations (0.01–0.2% w/w) using phosphate buffer (PB) or glycerol phosphate buffer (G-PB) as the hydration medium. These NaHA coated liposomes could have a potential in the treatment of dry mouth since glycerol and NaHA are known for their lubricating and hydrating properties. The liposomes composed of SoyPC-DOTAP 20 mol%, and coated with NaHA MW 90–130 kDa, 0.05% w/w were found to be most stable during storage. The liposomes with 20 mol% DOTAP coated with NaHA MW 30–50 kDa, 0.05% w/w showed promising results as these stayed stable for at least two weeks. However, the liposomes coated with NaHA MW 8–15 kDa were generally unstable irrespective of the combinations of the investigated parameters. When the stable liposomes were introduced into artificial saliva (AS), aggregation rapidly occurred. Sodium alginate (NaAlg) coated liposomes that were prepared for comparison were found to be stable in AS. The study has demonstrated the influence of the amount of charged lipid which must be high, the polymer MW which must lay in the area 30 kDa-130 kDa and coating concentration which should be intermediate 0.05% w/w in preparing stable NaHA coated liposomes. Further studies need to be conducted to understand the instability exhibited by the NaHA coated liposomes in AS.

Systematic Reviews on the Management of Xerostomia and Hyposalivation-An Umbrella Review.

Dry mouth is moderately prevalent in the older population. Pharmacological and non-pharmacological alternatives have been assessed to manage its manifestation. This umbrella review synthesised the evidence on approaches to managing xerostomia and hyposalivation. We searched for systematic reviews of interventions to manage dry mouth in Cochrane Database of Systematic Reviews, EMBASE, PubMed, Prospero and DARE databases (up to September 2023). References were managed and selected by reading titles and abstracts using Rayyan QCRI. Selection of studies, data extraction and methodological quality assessment (AMSTAR 2) were conducted independently, in duplicate. Data were extracted to a previously tested form that included information about dry mouth causes, interventions, outcomes and findings. There were 3323 records. At the end of the selection process, 48 studies were included and had data extracted. Only three high-quality systematic reviews were found to support methods for managing dry mouth. Limited evidence suggests that topical therapies offer significant palliative or stimulating effects for relieving dry mouth symptoms. Furthermore, low-quality evidence indicates a slight increase in saliva production with acupuncture, dry mouth prevention with amifostine, and saliva stimulation using pilocarpine in patients who have undergone head and neck radiotherapy. Salivary substitutes and stimulants mostly acted as moisturisers and some as saliva stimulants, with short-term effect. More than 80% of the reviews were appraised as 'critically low' quality. Well-designed and well-reported systematic reviews are still needed to increase the level of evidence on dry mouth management methods. Prospero Registration CRD42022325854.

A Population-Based Study of the Association Among Dry Mouth, Vitamin B2, and Mortality.

Previous studies have indicated that older adults with the symptom of dry mouth have an increased risk of death. B vitamins are strongly linked to oral and systemic health. However, the relationship among dry mouth, vitamin B2 and mortality remains unclear. This study aimed to investigate the potential relationship among dry mouth, vitamin B2 and mortality. A total of 6183 participants from the US National Health and Nutrition Examination Survey (NHANES) 2011-2014 with information on dry mouth were included at baseline. 4324 normal individuals and 684 individuals with dry mouth were followed up until 31 December 2019. The Cox proportional hazard model was used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) for the associations among dry mouth, vitamin B2 and all-cause mortality. Compared to the population without dry mouth, the risk of all-cause mortality was significantly higher in the population with dry mouth. The multivariable-adjusted HR and 95% CI was 1.41 (1.05, 1.90). The intake of vitamin B2 can significantly reduce the risk of death in participants with dry mouth, but not in participants without dry mouth. The HR and 95% CI of all-cause mortality in the highest vitamin B2 intake group was 0.37 (0.19, 0.73) compared to the lowest intake group. Individuals with dry mouth suffered a significantly higher risk of all-cause mortality compared to those without dry mouth. Higher intake of vitamin B2 was apparently associated with a lower risk of all-cause mortality in the population with dry mouth.

Management of radiotherapy-induced hyposalivation using photobiomodulation therapy: a case series.

It is not uncommon for individuals receiving radiotherapy for head and cancers to experience dry mouth sensation (xerostomia), salivary hypofunction (hyposalivation) and taste changes. The present study aimed to evaluate the short-term effectiveness of biweekly photobiomodulation therapy (PBMT) in managing these radiotherapy-induced adverse effects and its impact on oral health-related quality of life. Ten patients who developed xerostomia and hyposalivation secondary to radiotherapy for head and neck cancer were included. The study assessments included clinician-based [the stimulated (SSF) and unstimulated salivary flow (USSF) and taste change questionnaire] and patient-based measures [Shortened Xerostomia Inventory (SXI) and Oral Health Impact Profile (OHIP-5)]. The 10 participants (males = 5, females = 5) had a mean age of 52 (± 15) years. Half were diagnosed with nasopharyngeal squamous cell carcinoma. From visits 1 to 8, 80% showed increased USSF and/or SSF, but these were limited and not significant (p > 0.05). Nevertheless, 80% of the patients had lower xerostomia scores, 60% had less dryness frequency, and 40% showed taste improvement. Improvement in oral health-related quality of life was only observed in 30% of the participants. Strong proportional correlations were found between USSF and SSF as well as SXI and OHIP-5 at study visits 1 and 8 (p < 0.05). The findings showed the usefulness of PBMT in reducing xerostomia and taste changes and possibly increasing salivary flow over a 4-week duration. However, randomised clinical trials are needed to assess the long-term effectiveness of PBMT compared to other management options.Clinical study registration: The study was prospectively registered with the US National Library of Medicine's clinical trial registry on 13 September 2022 [ClinicalTrials.gov ref: NCT05538169].

Fecal metabolomic analysis of the role of gut microbiota and short-chain fatty acids in the therapeutic mechanism of Timosaponin AIII in Sjögren's syndrome.

Sjogren's syndrome (SS) is a chronic inflammatory and difficult-to-treat autoimmune disease. Timosaponin AIII (TAIII), a plant-derived steroidal saponin, effectively inhibits cell proliferation, induces apoptosis, and exhibits anti-inflammatory properties. This study explored the mechanisms of action of TAIII in SS treatment by studying gut microbiota and short-chain fatty acids (SCFAs) using fecal metabolomics. The model group used non-obese diabetic (NOD) mice. The treatment group was classified into TAIII and hydroxychloroquine groups. The gut microbiota, SCFAs, and metabolites were analyzed using 16S rRNA sequencing, gas chromatography-mass spectrometry analysis, and liquid chromatography-mass spectrometry, respectively. TAIII effectively alleviated dry mouth in NOD mice, slowed the progression of salivary gland tissue injury, reduced inflammatory factor expression, and increased the levels of aquaporins 1 and 5. TAIII regulated SCFA content and tryptophan metabolism by altering the abundance of the Rikenellaceae_RC9_gut_group, thereby reducing the inflammatory response. TAIII can improve imbalances in the gut microbiota and the metabolic levels of related SCFAs and tryptophan, thereby reducing the level of inflammation. The significant differences observed in the abundance of the Rikenellaceae_RC9_gut_group between the treatment and control groups indicated the potential relationship between bacteria and metabolites in SS. Key Points • The safe and effective treatment of SS with traditional Chinese medicine • Multi-means study on intestinal flora, short-chain fatty acids, and metabonomics.

A Review of the Impact of Sjögren's Syndrome and/or the Presence of Anti-Ro/SS-A Antibodies on Therapeutic Strategies for Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is an immune-mediated disease characterized by polyarthritis that affects the small joints of the bilateral upper and lower extremities. RA shares several common clinical symptoms with Sjögren's syndrome (SS), another rheumatic disease caused by the lymphocytic infiltration of exocrine glands, with dry eye and dry mouth being the two most common symptoms. Anti-Ro/SS-A antibodies, a diagnostic biomarker of SS, are positive in patients with RA at a certain rate. The coexistence of SS and/or positivity for anti-Ro/SS-A antibodies in patients with RA influences disease activity and the effectiveness of several classes of disease-modifying antirheumatic drugs (DMARDs). Furthermore, RA, SS, and certain DMARDs, including methotrexate, are associated with the onset of lymphoproliferative disorders (LPD). In contrast, several biological DMARDs, such as tocilizumab and rituximab, are plausible options without the risk of LPD relapse. Considering the results of the studies introduced in this article, RA with SS and/or positivity for anti-Ro/SS-A antibodies could be considered a phenotype different from isolated RA from the perspective of refractoriness to DMARD therapy and LPD risk. Hence, rheumatologists should observe caution when choosing DMARDs. Further studies are needed to establish the appropriate treatment for patients with RA, SS, and/or the presence of anti-Ro/SS-A antibodies.

Prevalence and Associations of Xerostomia in Older Adults in Southern Brazil.

This study investigated the prevalence and associations of xerostomia in older adults in southern Brazil. A cross-sectional study was carried out in Pelotas, Brazil, during 2014. A representative sample of the city's older adult population (60+) was selected. The dependent variable was self-reported feeling of dry mouth in the past 6 months. Covariates included socio-economic status, schooling, gender, age, tobacco and alcohol consumption, polypharmacy, hypertension, diabetes, arthritis, depression, dentition status and use of removable dental prostheses. Descriptive analysis was carried out, and Poisson regression was used to obtain prevalence ratios and 95% confidence intervals. Analyses used STATA 15.1. Most of the 1451 participants were female (63.3%). The prevalence of xerostomia was 36.7% (95% CI 34.3-39.1). Adjusted analysis showed that xerostomia was significantly more common among females (PR 1.44, 95% CI 1.22-1.74), those with less schooling (PR 1.31, 95% CI 1.10-1.51), those exposed to polypharmacy (PR 1.22, 95% CI 1.05-1.37), people with arthritis (PR 1.42, 95% CI 1.23-1.61) and those with depression symptoms (PR 1.45, 95% CI 1.23-1.70). Xerostomia is common among older adults. Health workers need to pay attention to its associated factors for early identification and promotion of appropriate interventions, particularly the rational use of medicines.

Exploring early postoperative core symptoms in Chinese patients with primary liver cancer: a cross-sectional and longitudinal network analysis.

Patients with primary liver cancer (PLC) experience a range of symptoms in the early postoperative period. Symptoms include cancer-related symptoms and adverse effects of treatment. Exploring the core symptoms and their dynamics in the early post-hepatectomy patients may help provide better symptom management programs. The purpose of this study was to identify the core symptoms in early post-hepatectomy patients and to explore the trajectory of their dynamics. During the period from March 2021 to September 2022, a total of 281 patients diagnosed with PLC and undergoing radical curative surgery were recruited from the hepatobiliary surgery departments of two hospitals in Eastern China, among whom 249 individuals (88.6%) agreed to participate in the study. A comprehensive symptom assessment was administered to the patients 1-2days after surgery (T1) and 1-2days before discharge (T2). Network analysis was used to identify core symptoms in early post-hepatectomy patients based on symptom severity. The network analysis identified the core symptoms of dry mouth, pain, abdominal distension, the lack of appetite, and nausea at T1. In contrast, at T2, the lack of appetite, pain, shortness of breath, and disturbed sleep were revealed. At the two early time points, while the results of the network structure test showed no statistically significant difference in the overall symptom network structure, there was a significant difference in the results for the core symptoms. Our study demonstrates the need to identify core symptoms in the early post-hepatectomy to improve symptom management in PLC patients. It is crucial to apply network analysis as an essential component of cancer care.

The Effect of Music Therapy on the Intellectual Disabilities Associated With Dry Mouth

The Effect of Music Therapy on the Intellectual Disabilities Associated With Dry Mouth

An Evaluation of Iloperidone for Mania in Bipolar I Disorder.

To review the efficacy of iloperidone for mania associated with bipolar I disorder and discuss its safety profile (eg, QTc prolongation, orthostatic hypotension, and metabolic adverse effects). Literature was identified using PubMed (1966-September 2024), OVID (1984-November 2024), and clinicaltrials.gov. Search terms included iloperidone, bipolar disorder, and mania. The study included trials evaluating iloperidone for treating bipolar mania. In one phase 3 study, iloperidone demonstrated significant improvement in mania symptoms at day 28 on all primary (ie, Young Mania Rating Scale) and secondary outcomes (Clinical Global Impression-Severity/Change scales) compared to placebo. Iloperidone was well tolerated, with tachycardia, dizziness, dry mouth, alanine aminotransferase elevation, nasal congestion, increased weight, and somnolence reported as common adverse effects. Since there are no head-to-head studies comparing iloperidone with other second-generation antipsychotics for bipolar mania, other treatment considerations drive medication selection. Iloperidone is unavailable in a generic formulation; thus, its use will be associated with higher costs. It is dosed twice daily, which may negatively impact adherence. Iloperidone is associated with a moderate risk of QTc prolongation, metabolic adverse effects, and orthostatic hypotension, which will limit its use in certain patient populations. QTc prolongation is dose related, so drug interactions involving CYP2D6 and CYP3A4 inhibition can have serious consequences. In the pivotal trial, iloperidone was effective in treating adults with an acute manic or mixed episode associated with bipolar I disorder and was safe and well tolerated.

Cross-Lagged Panel Network Analysis of Symptoms in Patients with Gastric Cancer Undergoing Postoperative Chemotherapy.

To develop temporal symptom networks at three postoperative chemotherapy time points and investigate the longitudinal relationships between 18 symptoms in patients with gastric cancer undergoing postoperative chemotherapy in China. Symptom prevalence and severity were measured using the M. D. Anderson Symptom Inventory (MDASI) and Gastrointestinal Cancer Module of the MDASI (MDASI-GI) at T1, T2, and T3 on the day after the first, third, and sixth chemotherapy sessions, respectively. Cross-lagged panel network (CLPN) models were employed to examine the temporal dynamics of the 18 symptoms and their interrelationships. In total, 379 participants were included. Dry mouth had the highest out-prediction (r = 0.101) and out-strength (r = 0.863) values during T1→T2. The strongest direct effect was observed for the change in taste → lack of appetite (β = 0.38) during T2→T3. Feeling bloated had the highest values for out-strength (r = 0.910), out-prediction (r = 0.215), and bridge strength (r = 1.010) during the T2→T3 period. The two CLPNs showed medium to high stability based on the centrality stability coefficients of out-strength and in-strength. Lack of appetite can be improved during chemotherapy by managing vomiting and taste changes. Attention should be paid to the dry mouth and feeling bloated, as they are the strongest predictors in the early and middle stages of treatment. Understanding the relationship between symptoms during chemotherapy in patients with postoperative gastric cancer can help clinicians identify targets for intervention at different times.

Safety and Satisfaction Analysis of Intravenous and Inhalational Conscious Sedation in a Geriatric Population Undergoing Oral Surgery.

Aim: The objective of this research was to compare two methods of conscious sedation (midazolam vs. sevoflurane) used for performing oral surgical procedures in the older adult population by analyzing dental treatment-related anxiety levels, the quality of sedation, and potential hemodynamic changes during the interventions, as well as post-recovery symptoms and patient satisfaction levels. Methods: A total of 104 patients underwent oral surgery with intravenous (age: 84.00 ± 8.410; 17 men and 36 women) and inhalation conscious sedation (age: 82.73 ± 8.809; 18 men and 33 women). Anxiety levels were recorded using the Modified Corah Dental Anxiety Scale (MDAS) and the Hamilton Anxiety Rating Scale (HARS). During the intervention, the heart rate, systolic/diastolic blood pressure, oxygen saturation, episodes of hypoxia (<90%SpO2), sedation duration, and Sedation-Agitation Scale (SAS) values were monitored. Upon completion of their treatment, all patients completed three questionnaires which evaluated their recall of the intervention, postoperative symptoms, and recommendation of the sedation method used. Results: Anxiety levels were slightly higher in the midazolam group (MDAS score: 9.60 ± 5.849; HARS score: 27.19 ± 6.802) compared to the sevoflurane group (MDAS score: 8.37 ± 5.063; HARS score: 24.92 ± 5.199), with no statistical significance (MDAS, p = 0.453/HARS, p = 0.065). No significant differences in the analyzed hemodynamic parameters were observed between the two groups. However, SAS values were significantly higher in the sevoflurane group (p = 0.006), while the sedation duration was longer in the midazolam group (p = 0.000). Postoperative symptoms, particularly gastrointestinal disturbances and dry mouth, were significantly more prevalent in the midazolam group, while there were no differences in neurological symptoms between the two groups. The majority of patients expressed a preference for either of these sedation methods. Conclusions: Sedation with agents such as midazolam and sevoflurane appears to be quite safe, given the absence of relevant hemodynamic changes. Midazolam has been shown to be effective for a longer duration, as well as to have a lower risk of developing greater digestive problems during the postoperative period. On the contrary, sevoflurane produced a greater sensation of dry mouth. Both sedative agents are perceived by the older adult population as satisfactory, recommending their use.

Probiotics Combined With Trimebutine for the Treatment of Irritable Bowel Syndrome Patients: A Systematic Review and Meta-Analysis.

This study aimed to assess the efficacy and safety of probiotics combined with trimebutine in the treatment of irritable bowel syndrome (IBS), addressing an important gap in current treatment strategies. Randomized controlled trials (RCTs) of trimebutine combined with probiotics for the treatment of IBS were collected from various databases. All retrieved articles were screened and assessed for quality. The methodological quality of the included studies was assessed following the guidelines recommended by the Cochrane Collaboration. The meta-analysis of the included studies was conducted using RevMan 5.3 software. A total of 37 RCTs involving 4360 participants were included in this study. Among them, the treatment group consisted of 2177 participants, and the control group consisted of 2183 participants. The results showed that the overall efficacy of trimebutine combined with probiotics in the treatment of IBS was significantly higher than that of trimebutine alone (odds ratio [OR] = 5.09, 95 % confidence interval [CI] [4.19, 6.20], p < 0.00001). The effective rate in the combination therapy group was 93.5 % compared with 73.8 % in the trimebutine alone group. The safety profile was favorable, with adverse event rates of 1.75 % and 1.69 % in the combination and monotherapy groups, respectively. The most common adverse events were mild and included dry mouth, nausea and dizziness. No serious adverse events were reported in either group. Subgroup analysis based on the type of probiotic intervention showed that combination use was better than trimebutine alone, and the differences between each subgroup were statistically significant. Combination use of compound Lactobacillus capsules had the best effect (OR = 16.03, 95 % CI [4.57, 56.21], p < 0.0001]. These results highlight the potential role of strain-specific benefits in IBS treatment and suggest that probiotic strain selection may significantly influence treatment outcomes. The combination of trimebutine and probiotics is more effective in the treatment of IBS compared with trimebutine alone. https://www.crd.york.ac.uk/prospero/, identifier: CRD42024516044.

ANALYSIS OF MULTISYSTEMIC MANIFESTATIONS OF SJÖGREN'S SYNDROME: A FOCUS ON DERMATO-OPHTHALMOLOGICAL INTERRELATIONS

Sjögren’s Syndrome (SS) is a systemic autoimmune disease known for its hallmark symptoms of dry eye and dry mouth, but it also presents a spectrum of extraglandular manifestations affecting the skin, lungs, nervous system, and other organs. This systematic review examines the multisystemic impacts of SS, highlighting advancements in diagnostics, therapeutic strategies, and clinical challenges. A comprehensive search was conducted across PubMed, MEDLINE, and Embase for studies published between 2013 and 2024, using keywords such as "Sjögren’s Syndrome," "Multisystemic Manifestations," "Autoimmune Disease," and "Extraglandular Complications." Of the 56 initially identified articles, 13 met the inclusion criteria. Findings reveal that pulmonary complications, including interstitial lung disease, occur in 9–20% of SS cases, as reported by Flament et al. (2016), emphasizing the importance of imaging and biopsy for early detection. Dermatological manifestations, such as vacuolar interface dermatitis and vasculitis, were detailed in studies by El Hasbani et al. (2023) and Kakurai et al. (2021), which underscore the need for dermatological vigilance in systemic autoimmune diseases. Neurological symptoms, including peripheral neuropathies and neuropsychiatric complications, were identified as early indicators in studies by Posso-Osorio et al. (2019) and Salehi et al. (2024), suggesting that such presentations require immediate multidisciplinary evaluation. Therapeutic advancements include the use of corticosteroids, hydroxychloroquine, and biologic agents such as rituximab, which have shown efficacy in managing systemic manifestations. Chu et al. (2020) emphasized the benefits of immunosuppressive therapy in improving systemic outcomes while acknowledging the limited efficacy for glandular symptoms. Advanced diagnostic tools like PET/CT, explored by Sharma and Chatterjee (2015), have improved diagnostic precision, aiding in the differentiation of SS from other systemic conditions. Despite these advancements, challenges remain in addressing disease heterogeneity and atypical presentations, particularly in men, children, and patients without classic glandular involvement. Standardized diagnostic protocols and tailored therapeutic strategies are needed to improve outcomes and reduce the burden of extraglandular complications.

Initial clinical experience with [177Lu]Lu-PNT2002 radioligand therapy in metastatic castration-resistant prostate cancer: dosimetry, safety, and efficacy from the lead-in cohort of the SPLASH trial.

SPLASH (NCT04647526) is a multicenter phase III trial evaluating the efficacy and safety of [177Lu]Lu-PNT2002 radioligand therapy in metastatic castration-resistant prostate cancer (mCRPC). This study leveraged a lead-in phase to assess tissue dosimetry and evaluate preliminary safety and efficacy, prior to expansion into a randomized phase. Here we report those results. Enrolled participants had mCRPC that progressed on one prior androgen receptor pathway inhibitor (ARPI), were prostate-specific membrane antigen (PSMA) PET-positive as determined by a central reader, were chemotherapy-naïve for mCRPC, and had adequate bone marrow and end-organ reserve. Participants received up to 4 cycles of [177Lu]Lu-PNT2002 at 6.8 GBq (± 10%) intravenously per cycle every 8 weeks. Dosimetry (planar + SPECT/CT [n=7]; planar only [n=20]), safety, prostate-specific antigen (PSA) response, objective response rate (ORR), and radiographic progression-free survival (rPFS) per blinded independent central review were assessed. Of 34 individuals screened, 32 underwent PSMA-PET/CT; 27 met all eligibility criteria. Median (range) age was 72 (57-86) years; all participants were enrolled in North America; 40.7% initiated prior ARPI treatment without distant metastases (M0) and 25.9% while hormone sensitive. Nineteen of 27 (70.4%) participants completed all 4 planned cycles. Organs receiving the largest mean (median, range) specific absorbed doses were lacrimal glands at 1.2 (0.9, 0.4-6.7) Gy/GBq (planar only [n=27]), followed by kidneys at 0.73 (0.63, 0.22-1.8) Gy/GBq (planar + SPECT/CT [n=7]; planar only [n=20]). Mean (median, range) tumor specific absorbed dose was 4.3 (2.1, 0.3-33.4) Gy/GBq (approximately 29 Gy/cycle) based on planar + SPECT/CT of 21 lesions in seven participants. [177Lu]Lu-PNT2002 was associated with no treatment-related deaths, few treatment-related grade ≥3 treatment-emergent adverse events (TEAEs), and no discontinuations for unacceptable toxicity. Treatment-related TEAEs occurring in ≥10% of participants included dry mouth (22.2%; all grade 1), fatigue (18.5%; grades 1-2), nausea (18.5%; grades 1-2), and anemia (14.8%; grades 1-3). Median (95% CI) rPFS was 11.5 (9.2-19.1) months, a PSA decline of ≥50% occurred in 42.3% (11/26) of participants, and confirmed ORR for evaluable disease was 50% (5/10). [177Lu]Lu-PNT2002, administered at 6.8 GBq/cycle for 4 cycles, demonstrated a favorable dosimetry and safety profile, as well as promising preliminary efficacy. https://clinicaltrials.gov/, identifier NCT04647526.

Cerebral venous thrombosis as a rare complication of Sjögren's syndrome: case series and literature review.

As few cerebral venous thrombosis (CVT) patients with primary Sjögren's syndrome (pSS) have been reported, little is known about the characteristics of this rare complication. This study is aimed at describing the clinical features, treatment, and outcome of CVT combined with pSS. We reported five patients of CVT and pSS admitted to our hospital and searched the relevant case reports in PubMed for literature review. We reviewed a total of twelve patients with pSS and CVT. Among them, five patients were from our report in the present paper, and seven other patients were from the case reports searched in PubMed. In total twelve patients, eleven patients were female. The twelve patients had an average age of 43.7 ± 8.3years (age range, 26-57years). The symptoms of pSS included multiple caries (50%), dry mouth (41.7%), dry eyes (33.3%), arthritis symptoms (16.7%), and parotid gland swelling (8.3%). Headache was the most common neurological symptom in all patients. Four patients (33.3%) had no clinical symptoms associated with pSS. Anti-SSA antibodies were positive in all patients. Antiphospholipid antibodies (aPLs) were positive in 33.3% of patients. Unilateral transverse sinus (75.0%) was the most commonly involved venous sinus. All patients received anticoagulant therapy. Hydroxychloroquine was also administered to the patients. Seven patients were treated with glucocorticoids. All patients recovered completely with no clinical or radiological recurrence. pSS combined with CVT is a rare condition. Middle-aged women with pSS should be alert to the presence of CVT. It is of great importance to screen for autoimmune diseases during the clinical course of CVT, especially in patients with unilateral transverse sinus thrombosis. Effective treatment strategies require further study. Key Points • Patients combined with CVT are very rare. • Screening for autoimmune diseases in CVT patients is great important. • Patients may have good prognosis when effective treatment is administrated.

Immune Profile Differences between IgG4-Related Diseases and Primary Sjögren's Syndrome.

Immunoglobulin G4-related disease (IgG4-RD) share clinical features with primary Sjögren's syndrome (pSS). This study aimed to identify altered serological parameters and potential biomarkers of IgG4-RD and pSS. Forty IgG4-RD patients, 40 pSS patients, and 40healthy controls (HC) were enrolled in this study. Routine serological parameters and clinical manifestations were assessed. IgG subclasses (IgGSc) were detected using a Siemens BN P, and lymphocyte subsets were analyzed using flow cytometry. Cytokines assays were performed using cytometric bead array. Compared to pSS, IgG4-RD patients had higher IgG4 (p <0.001) and lower IgG1 (p =0.014). The natural killer (NK) cells (p = 0.004), CD4+ T cells (p = 0.028), and TBNK cells (p = 0.040) were increased in IgG4-RD compared to pSS. IgG4 used to differentiate IgG4-RD from pSS produced an area under the curve (AUC) of up to 0.952. In addition, we compared serum parameters, immune cells, and cytokines of IgG4-RDwith mouth dryness or eye dryness with those of pSS with the same symptoms, and similar serological changes were observed. IgG4-RD patients with mouth dryness had higher IgG4 (p <0.001) and Th cells (p = 0.016) but lower IgG1 (p = 0.009) compared to pSS with dry mouth. IgG4-RD patients with eye dryness had higher levels of IgG4 (p <0.001), Treg cells (p = 0.037), and NK cells (p = 0.017) than pSS patients with eye dryness. Moreover, IgG4-RD patients with mouth and eye dryness had higher levels of B (p = 0.006), Th (p = 0.026), Th2 (p = 0.007), and Treg cells (p = 0.028) than IgG4-RD patients without mouth and eye dryness. Immune system disorder is an outstanding feature of IgG4-RD, and its feature differ from pSS. Assessment of immune status is important in the diagnosis and differential diagnosis of IgG4-RD.

A Case of Hepatocellular Carcinoma Complicated by Fulminant Type 1 Diabetes Mellitus Shortly After Initiation of Durvalumab Plus Tremelimumab

A 64-year-old man with cirrhosis was diagnosed with unresectable hepatocellular carcinoma and treated with a combination of durvalumab and tremelimumab. The patient had no history of diabetes mellitus. Three weeks later, the patient developed general fatigue, dry mouth, and polyuria. A subsequent blood examination revealed a blood glucose level of 706 mg/dL and C-peptide level of 0.29 ng/mL, with an HbA1c of 6.4%. The patient was diagnosed with fulminant type 1 diabetes mellitus. Although fulminant type 1 diabetes mellitus is a rare immune-mediated adverse event, it requires prompt attention shortly after the initiation of these agents owing to its severe and emergent nature.