Na+/K+-ATPase (NKA) is abundantly expressed in the basolateral membrane of epithelial cells, which is necessary for tight junction formation. The tight junction is an urothelial barrier between urine and the underlying bladder. Impairment of tight junctions allows migration of urinary solutes in patients with interstitial cystitis/painful bladder syndrome (IC/PBS). We evaluated NKA expression and activity in bladder samples from patients with IC/PBS. The study group consisted of 85 patients with IC/PBS, and the control group consisted of 20 volunteers. Bladder biopsies were taken from both groups. We determined the expression and distribution of NKA using NKA activity assays, immunoblotting, immunohistochemical staining, and immunofluorescent staining. The protein levels and activity of NKA in the study group were significantly lower than the control group (1.08 ± 0.06 vs. 2.39 ± 0.29 and 0.60 ± 0.04 vs. 1.81 ± 0.18 micromol ADP/mg protein/hour, respectively; P < 0.05). Additionally, immunofluorescent staining for detection of CK7, a marker of the bladder urothelium, predominantly colocalized with NKA in patients in the study group. Our results demonstrated the expression and activity of NKA were decreased in bladder biopsies of patients with IC/PBS. These findings suggest that NKA function is impaired in the bladders from patients with IC/PBS.
Adult ; Cystitis, Interstitial/*diagnosis/metabolism ; Female ; Fluorescent Antibody Technique ; Humans ; Keratin-7/metabolism ; Male ; Microscopy, Fluorescence ; Middle Aged ; Sodium-Potassium-Exchanging ATPase/*metabolism ; Urinary Bladder/metabolism/pathology ; Urothelium/metabolism/pathology

Background/Aims: Laryngeal symptoms are largely treated with empiric proton pump inhibitor (PPI) therapy if no apparent pathology shown on ear, nose, and throat evaluation and reflux-related etiologies are suspected. However, treatment response remains unsatisfactory. This study aimed to investigate the clinical and physiological characteristics of patients with PPI-refractory laryngeal symptoms. Methods: Patients with persistent laryngeal symptoms despite PPI treatment for ≥ 8 weeks were recruited. A multidisciplinary evaluationcomprising validated questionnaires for laryngeal symptoms (reflux symptom index [RSI]), gastroesophageal reflux disease symptoms, psychological comorbidity (5-item brief symptom rating scale [BSRS-5]) and sleep disturbance (Pittsburgh sleep quality index [PSQI]), esophagogastroduodenoscopy, ambulatory impedance-pH monitoring, and high-resolution impedance manometry were performed.Healthy asymptomatic individuals were also recruited for comparison of psychological morbidity and sleep disturbances. Results: Ninety-seven adult patients and 48 healthy volunteers were analyzed. The patients had markedly higher prevalence of psychological distress (52.6% vs 2.1%, P < 0.001) and sleep disturbance (82.5% vs 37.5%, P < 0.001) than the healthy volunteers. There were significant correlations between RSI and BSRS-5 scores, and between RSI and PSQI scores (r = 0.26, P = 0.010, and r = 0.29, P = 0.004, respectively). Fifty-eight patients had concurrent gastroesophageal reflux disease symptoms. They had more prominent sleep disturbances (89.7% vs 71.8%, P < 0.001) than those with laryngeal symptoms alone but similar reflux profiles and esophageal motility. Conclusions PPI-refractory laryngeal symptoms are mostly associated with psychological comorbidities and sleep disturbances. Recognition of these psychosocial comorbidities may help optimize management in these patients.

BACKGROUND: This study investigated whether xenotransplantation of human Wharton’s jelly-derived mesenchymal stem cells (WJ-MSCs) reduces thioacetamide (TAA)-induced mouse liver fibrosis and the underlying molecular mechanism. METHODS: Recipient NOD/SCID mice were injected intraperitoneally with TAA twice weekly for 6 weeks before initial administration of WJ-MSCs. Expression of regenerative and pro-fibrogenic markers in mouse fibrotic livers were monitored post cytotherapy. A hepatic stallate cell line HSC-T6 and isolated WJ-MSCs were used for in vitro adhesion, migration and mechanistic studies. RESULTS: WJ-MSCs were isolated from human umbilical cords by an explant method and characterized by flow cytometry. A single infusion of WJ-MSCs to TAA-treated mice significantly reduced collagen deposition and ameliorated liver fibrosis after 2-week therapy. In addition to enhanced expression of hepatic regenerative factor, hepatocyte growth factor, and PCNA proliferative marker, WJ-MSC therapy significantly blunted pro-fibrogenic signals, including Smad2, RhoA, ERK. Intriguingly, reduction of plasma fibronectin (pFN) in fibrotic livers was noted in MSC-treated mice. In vitro studies further demonstrated that suspending MSCs triggered pFN degradation, soluble pFN conversely retarded adhesion of suspending MSCs onto type I collagen-coated surface, whereas pFN coating enhanced WJ-MSC migration across mimicked wound bed. Moreover, pretreatment with soluble pFN and conditioned medium from MSCs with pFN strikingly attenuated the response of HSC-T6 cells to TGF-b1-stimulation in Smad2 phosphorylation and RhoA upregulation. CONCLUSION These findings suggest that cytotherapy using WJ-MSCs may modulate hepatic pFN deposition for a better regenerative niche in the fibrotic livers and may constitute a useful anti-fibrogenic intervention in chronic liver diseases.

BACKGROUND: This study investigated whether xenotransplantation of human Wharton’s jelly-derived mesenchymal stem cells (WJ-MSCs) reduces thioacetamide (TAA)-induced mouse liver fibrosis and the underlying molecular mechanism. METHODS: Recipient NOD/SCID mice were injected intraperitoneally with TAA twice weekly for 6 weeks before initial administration of WJ-MSCs. Expression of regenerative and pro-fibrogenic markers in mouse fibrotic livers were monitored post cytotherapy. A hepatic stallate cell line HSC-T6 and isolated WJ-MSCs were used for in vitro adhesion, migration and mechanistic studies. RESULTS: WJ-MSCs were isolated from human umbilical cords by an explant method and characterized by flow cytometry. A single infusion of WJ-MSCs to TAA-treated mice significantly reduced collagen deposition and ameliorated liver fibrosis after 2-week therapy. In addition to enhanced expression of hepatic regenerative factor, hepatocyte growth factor, and PCNA proliferative marker, WJ-MSC therapy significantly blunted pro-fibrogenic signals, including Smad2, RhoA, ERK. Intriguingly, reduction of plasma fibronectin (pFN) in fibrotic livers was noted in MSC-treated mice. In vitro studies further demonstrated that suspending MSCs triggered pFN degradation, soluble pFN conversely retarded adhesion of suspending MSCs onto type I collagen-coated surface, whereas pFN coating enhanced WJ-MSC migration across mimicked wound bed. Moreover, pretreatment with soluble pFN and conditioned medium from MSCs with pFN strikingly attenuated the response of HSC-T6 cells to TGF-b1-stimulation in Smad2 phosphorylation and RhoA upregulation. CONCLUSION These findings suggest that cytotherapy using WJ-MSCs may modulate hepatic pFN deposition for a better regenerative niche in the fibrotic livers and may constitute a useful anti-fibrogenic intervention in chronic liver diseases.

Background: Ingestion of foreign bodies leading to impaction at the pharynx and oesophagus have been extensively described in English literatures. However, impactions at the gastrointestinal tract distal to the oesophagus are less commonly encountered due to the more capacious luminal diameter as it approaches the stomach. While intentional foreign body ingestions impacted distal to the oesophagus are often more complicated, literatures on the management of these distal oesophageal impactions are scarce. Case presentation: We present five cases of foreign body impaction at varying sites of gastrointestinal tract beyond the oesophagus, contrasting management approach comparing the role of endoscopy, open surgery and conservative management. Cases presented include patients aged 40 to 70 with intentional foreign bodies ingestion. The first case described a cerebral palsy patient with pica who had to undergo difficult evacuation under anaesthesia followed by colonoscopy; the second and third cases presented 2 different schizophrenic patients with 2 differing management approach. The second case was managed with multiple operations due to complications and died eventually, making the only mortality in our case series; whereas the third case was managed conservatively with acceptable outcome after multiple laparotomies prior. Fourth and fifth cases described 2 body packers who swallowed tobacco and 2 phones, respectively; the former was uneventfully managed conservatively, the latter, had to undergo surgical extraction. Individualized approach to these distal impactions of ingested foreign bodies are described with a review of available literatures which are tabulated and discussed in this case series. Conclusion Endoscopy, surgery, conservative management and sometimes a combination of approaches are utilised for the management of foreign bodies impacted distal to the oesophagus, especially in complex and recurrent cases. Decision, timing and approach of extraction must be individualised with consideration of risk weighed against the benefit of each intervention over the other

Purpose: Numerous guidelines have been proposed in managing surgical emergencies during COVID-19 pandemic. Literature on the implications of these adjustments during this pandemic remained limited. This review aims to examine the implications of these critical adjustments with focus on appendicitis management. Method: This is a single-centre retrospective observational study in a Malaysian tertiary state surgical centre and review of recent guidelines and literature. Patients with appendicitis from March to May 2020 were included and medical records were reviewed and analysed. Results: Of the 173 appendicitis patients, 117 (67.6%) were operated and 56 (32.4%) were conservatively treated. Those screened for SARS-CoV-2 pre-operatively showed longer wait for operation (3.0 vs 2.0 days, p=0.001) and a longer hospital stay (4.5 vs 4.0 days, p=0.005). One-third of patients screened (36.6%) were expedited for surgery on clinical suspicion of complicated appendicitis and 42.1% progressed from acute to complicated appendicitis while waiting for screening result. All patients screened were COVID-19 negative. Delay due to SARS-CoV-2 screening did not result in worse outcome for appendicitis patients. Conclusion With the increase in incidence and rise of COVID-19 cases, routine screening by questionnaire, physical examination and naso-oropharyngeal swab may be considered to detect asymptomatic carrier, especially in regions with high infection. Regular reassessment with low threshold to expedite the surgery is necessary, to ensure satisfactory surgical outcome.

Blunt traumatic tracheobronchial injury is rare, but can be potentially life-threatening. It accounts for only 0.5%-2% of all trauma cases. Patients may present with non-specific signs and symptoms, requiring a high index of suspicion with accurate diagnosis and prompt treatment. A 26-year-old female was brought into the emergency department after sustained a blunt trauma to the chest from a high impact motor vehicle accident. She presented with signs of respiratory distress and extensive subcutaneous emphysema from the chest up to the neck. Her airway was secured and chest drain was inserted for right sided pneumothorax. CT of the neck and thorax revealed a collapsed right middle lung lobe with a massive pneumothorax, raising the suspicion of a right middle lobe bronchus injury. Diagnosis was confirmed by bronchoscopy. In view of the difficulty in maintaining her ventilation and persistent pneumothorax with a massive air leak, immediate right thoracotomy via posterolateral approach was performed. The right middle lobar bronchus tear was repaired. There were no intra- or post-operative complications. She made an uneventful recovery. She was asymptomatic at her first month follow-up. A repeated chest X-ray showed expanded lungs. Details of the case including clinical presentation, imaging and management were discussed with an emphasis on the early uses of bronchoscopy in case of suspected blunt traumatic tracheobronchial injury. A review of the current literature of tracheobronchial injury management was presented.
Humans ; Female ; Adult ; Pneumothorax/surgery* ; Bronchi/injuries* ; Wounds, Nonpenetrating/diagnosis* ; Bronchoscopy ; Trachea/injuries*