Does Prehabilitation Reduce Postoperative Length of Hospital Stay after Esophageal Cancer Surgery?

Objectives: At our hospital, prehabilitation has been provided to patients undergoing esophageal cancer surgery since October 2019. This study explored the effects of prehabilitation based on the accumulated database of these patients. Methods: This retrospective cohort study included 621 patients who underwent thoracoscopic subtotal esophagectomy. Multiple linear regression analysis was performed using postoperative hospital stay as the objective variable and age, sex, body mass index (BMI), preoperative ventilatory impairment, left ventricular ejection fraction, preoperative hemoglobin A1c, clinical stage, histological type, operative time, surgical blood loss, postoperative complications, and prehabilitation as explanatory variables. We also performed a multivariate analysis in the subgroup of patients who developed postoperative complications and adjusted for possible confounding factors. Postoperative complications and postoperative hospital stay were compared between patients without (n=416) and with (n=205) prehabilitation. Results: Postoperative complications, age, blood loss, BMI, and ventilatory impairment influenced the overall length of hospital stay. When the analysis was restricted to patients with complications, prehabilitation was added to that list of factors as a substitute for BMI. The rate of postoperative complications was not affected by prehabilitation (P=0.1675). The number of hospital days did not change with or without prehabilitation in the overall population, but when restricted to patients with complications, the number of hospital days was significantly decreased in the prehabilitation group (P=0.0328). Conclusions: Prehabilitation as a perioperative approach has the potential to reduce the postoperative length of hospital stay in patients undergoing esophageal cancer surgery, and active intervention is recommended.

Case of Moxifloxacin-Induced Black Hairy Tongue.

BACKGROUND Black hairy tongue (BHT) is a relatively uncommon acquired benign condition, with a prevalence ranging from 0.6% to 11.3%. It presents as a superficial black hairy carpet-like lingual growth. The exact etiology of BHT remains unclear, and both extrinsic and intrinsic factors are potentially contributive. Several types of antibiotics are also associated with BHT, but no English reports of moxifloxacin-induced BHT exist. Here, we report the first case of moxifloxacin-induced BHT. CASE REPORT A 69-year-old woman presented with a brown and hairy tongue. She was taking prednisolone for mixed connective tissue disease and developed right finger flexor tenosynovitis, which was complicated by osteomyelitis due to Mycobacterium chelonae. Based on the susceptibility results, she was treated with tobramycin, imipenem, and clarithromycin for 6 weeks, and then switched to moxifloxacin and clarithromycin. Within 10 days, she developed brown discoloration on the dorsum of the tongue, with carpet-like elongated filiform lingual papillae. The diagnosis of BHT was made. After stopping moxifloxacin, improvement was seen within 2 days, and her right finger has shown no signs of recurrence for 12 months. CONCLUSIONS Clinicians should be vigilant against agents and lifestyles that can precipitate BHT, especially moxifloxacin. It is essential to counsel patients before such treatments to avoid patient anxiety or treatment changes.

Tubulointerstitial nephritis in antineutrophil cytoplasmic antibody-associated vasculitis with monoclonal gammopathy.

Isolated tubulointerstitial nephritis (TIN) without glomerular crescent formation is a rare manifestation of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). Some patients with monoclonal gammopathy of undetermined significance present with renal complications due to serum monoclonal protein. Here, we present a case of TIN presumably attributable to AAV with monoclonal gammopathy. Laboratory data revealed acute kidney injury, elevated C-reactive protein (CRP) and ANCA titers, and elevated tubular injury markers. Renal biopsy revealed TIN with no apparent glomerular lesion. The findings of peritubular capillaritis and tubulitis indicated that AAV had contributed to the development of TIN. However, in situ hybridization for free light chains revealed kappa light chain restriction, indicating that the involvement of monoclonal gammopathy in the pathogenesis of TIN remains possible. The patient also developed ophthalmic neuropathy, probably caused by AAV. Oral prednisone (0.6 mg/kg/day) administration improved both the ocular symptoms and the laboratory parameters. Our case demonstrated that the concurrence of AAV and monoclonal gammopathy could pose a diagnostic dilemma in distinguishing the cause of TIN. Besides, some reports suggest an association between AAV and monoclonal gammopathy, although direct evidence is lacking. Further research is needed to establish this association.

Methylenation for Aldehydes and Ketones Using 1-Methylbenzimidazol-2-yl Methyl Sulfone.

The methylenation reagent 1-methylbenzimidazol-2-yl methyl sulfone 2 reacts with various aldehydes and ketones in the presence of t-BuOK (room temperature, 1 h) in dimethylformamide to give the corresponding terminal alkenes generally in high yields. For sensitive substrates, the reaction is better carried out at low temperature using sodium hexamethyldisilazide in 1,2-dimethoxyethane. The byproduct is easily removed from the products, and the reaction conditions are mild and practical. Reagent 2 can be easily prepared from commercially available 2-mercaptobenzimidazole 5 in 95% yield without any expensive reagents.

Different Effects on Fluid Distribution between Tolvaptan and Furosemide in a Liver Cirrhosis Patient with Chronic Kidney Disease.

A 73-year-old man with liver cirrhosis and advanced chronic kidney disease was admitted to our hospital due to bilateral lower leg edema and appetite loss. Furosemide to treat fluid retention markedly decreased extracellular water compared with intracellular water, but the addition of tolvaptan equally decreased both with a greater diuretic response than furosemide alone. Furthermore, tolvaptan administration increased the plasma colloid osmotic pressure, which might facilitate the shift of fluid from the extravascular space to the intravascular space. This is the first case showing different effects on the fluid distribution between furosemide and additional tolvaptan in the same patient.

Hemolytic Uremic Syndrome: An Increasingly Recognized Public Health Problem.

A 28-year-old man was referred and admitted to our hospital due to Escherichia coli O157-mediated hemorrhagic colitis with severe thrombocytopenia. A systemic workup concluded that the patient had acute pancreatitis as well as hemolytic uremic syndrome. The patient was ultimately discharged, with his platelet count having recovered. Our case serves an illustrative example of potentially serious complications of an increasingly recognized public health problem. Systemic studies on this topic are insufficient, and we strongly recommend the further accumulation of more experiences like ours. Several diagnostic and management concerns that emerged in this case are also discussed.

Valacyclovir Neurotoxicity and Nephrotoxicity in an Elderly Patient Complicated by Hyponatremia.

A 66-year-old women with no history of renal disease was admitted due to a coma and acute kidney injury with a serum creatinine level of 7.44 mg/dL which were ascribed to valacyclovir neurotoxicity and nephrotoxicity, respectively. She had received valacyclovir at a standard dosage for the treatment of herpes zoster and was finally discharged, having fully returned to her normal baseline mental status with a recovered serum creatinine level of 0.68 mg/dL. We feel that awareness of this pathology remains a challenge for physicians and therefore strongly recommend the further accumulation of experiences similar to our own. Our experience underscores the pitfalls of administering valacyclovir to elderly patients who barely appear to have a favorable renal function. Several concerns regarding the therapeutic management, including blood purification strategies, that emerged in this case are also discussed.

Pleuroperitoneal Communication and Ovarian Cancer Complicating Peritoneal Dialysis: A Case Report of a Patient with End-Stage Kidney Disease.

Peritoneal dialysis has been a widely accepted modality for treating end-stage kidney disease, but a regular dialysis schedule can be seriously disrupted by various comorbid conditions requiring surgical intervention. A 40-year-old woman who had been receiving peritoneal dialysis was sequentially but separately complicated by pleuroperitoneal communication and ovarian cancer. Despite the need for temporary interruption of her peritoneal dialysis schedule, it was successfully resumed after the relevant surgeries for each disease. Several concerns regarding overall postoperative dialytic management strategies, including how to deal with the peritoneal dialysis catheter during the postoperative period as well as how long peritoneal dialysis should be interrupted, which remain an unresolved issue in the field of nephrology, are also discussed.

Nephrotic Syndrome and a Retroperitoneal Mass: A Case Report of a Patient with Recurrent Invasive Thymoma.

A 68-year-old man was admitted to our hospital to undergo an examination for nephrotic syndrome while concurrently complicated with recurrent thymoma in the parietal pleura and retroperitoneum. He had been diagnosed with invasive thymoma and had undergone thymo-thymectomy seven years previously. Based on the renal biopsy findings, his nephrotic syndrome was ascribed to minimal change disease. He was treated with corticosteroid monotherapy, which resulted in complete remission six months later, despite the fact that the recurrent thymoma remained. The role of thymoma in the pathogenesis of paraneoplastic glomerulopathy and the therapeutic concerns that emerged in this case are also discussed.

Performing Anticoagulation: A Puzzling Case of Cholesterol Embolization Syndrome.

The avoidance of any form of anticoagulation is advised in cases of cholesterol embolization syndrome (CES). We herein describe a case of CES in a man with a history of unprovoked pulmonary embolism for which warfarinization was performed. Despite anecdotal reports of successful anticoagulation in CES patients with certain indications, irreversible renal failure, which was sufficiently severe to require chronic hemodialysis, eventually developed in our patient. Our results emphasize the pitfalls of this procedure, which imply its limited feasibility and safety. Several therapeutic concerns associated with this case are also discussed.

Dual Impact of Tolvaptan on Intracellular and Extracellular Water in Chronic Kidney Disease Patients with Fluid Retention.

Objective Tolvaptan, an oral selective V2-receptor antagonist, is a water diuretic that ameliorates fluid retention with a lower risk of a worsening renal function than conventional loop diuretics. Although loop diuretics predominantly decrease extracellular water (ECW) compared with intracellular water (ICW), the effect of tolvaptan on fluid distribution remains unclear. We therefore examined how tolvaptan changes ICW and ECW in accordance with the renal function. Methods Six advanced chronic kidney disease patients (stage 4 or 5) with fluid retention were enrolled in this study. Tolvaptan (7.5 mg/day) added to conventional diuretic treatment was administered to remove fluid retention. The fluid volume was measured using a bioimpedance analysis device before (day 0) and after (day 5 or 6) tolvaptan treatment. Results Body weight decreased by 2.6%±1.3% (64.4±6.5 vs. 62.8±6.3 kg, p=0.06), and urine volume increased by 54.8%±23.9% (1,215±169 vs. 1,709±137 mL/day, p=0.03) between before and after tolvaptan treatment. Tolvaptan significantly decreased ICW (6.5%±1.5%, p=0.01) and ECW (7.5%±1.4%, p=0.02), which had similar reduction rates (p=0.32). The estimated glomerular filtration rate remained unchanged during the treatment (14.6±2.8 vs. 14.9±2.7 mL/min/1.732 m, p=0.35). Conclusion Tolvaptan ameliorates body fluid retention, and induces an equivalent reduction rate of ICW and ECW without a worsening renal function. Tolvaptan is a novel water diuretic that has a different effect on fluid distribution compared with conventional loop diuretics.

Subclinical growth of an arteriovenous fistula associated with renal biopsy: a case report.

BACKGROUND: Renal biopsy is not free from complications and patients who undergo this procedure are usually hospitalized to receive intensive care for several days after biopsy. In contrast, after this period, routine follow-up to detect biopsy-associated complications is rarely scheduled, unless the patient develops a clinical manifestation. We describe a case of marked enlargement of arteriovenous fistula in the kidney that occurred many years after renal biopsy. In contrast to the previous cases requiring interventional radiology, our patient showed subclinical growth of fistula over about nine years. CASE PRESENTATION: A 24-year-old man with a history of percutaneous renal biopsy was hospitalized for interventional radiology. Gross hematuria emerged shortly after biopsy, but completely disappeared with administration of hemostatic agents and bed rest. Subsequently, the patient had few symptoms for many years. A giant fistula (a gourd-shaped mass, size 26 × 22 and 12 × 11 mm) was unexpectedly detected by ultrasonography performed for examination of an unrelated disorder (slight elevation of serum transaminase) at 9 years after the original biopsy. The fistula was successfully treated with radiological intervention. Thus, subclinical development of complications associated with renal biopsy should be considered, even in an uneventful course. CONCLUSIONS: This case provides a platform to discuss the importance of long-term follow-up of patients after renal biopsy despite of its difficulty.

Tubulointerstitial Nephritis and Uveitis Syndrome: Are Drugs Offenders or Bystanders?

A 16-year-old female patient was admitted to our hospital due to progressive renal dysfunction with an increased serum creatinine (sCr) level of 1.7 mg/dL. Her clinical course without any ocular manifestations and results of drug-induced, lymphocyte-stimulating tests, in addition to a renal histological assessment, initially encouraged us to ascribe the patient's renal abnormalities to drug-induced acute interstitial nephritis (AIN). Four months later, she started to complain about reduced visual acuity when she was found to have anterior bilateral uveitis despite the recovered renal function with almost constant sCr levels around 0.7 mg/dL. Thus, a diagnosis of tubulointerstitial nephritis and uveitis (TINU) syndrome was finally made. Our case illustrates the difficulties in distinguishing late-onset uveitis TINU syndrome from drug-induced AIN at the time of the renal biopsy, thereby suggesting the importance of a longitudinal follow-up to overcome the potential underdiagnosis of the disease. Several diagnostic conundrums that emerged in this case are also discussed.

Practical methylenation reaction for aldehydes and ketones using new Julia-type reagents.

A new Julia-type methylenation reagent, 1-methyl-2-(methylsulfonyl)benzimidazole (1e), reacts with a variety of aldehydes and ketones in the presence of either NaHMDS (-55 °C to rt) or t-BuOK (rt, 1 h) in DMF to give the corresponding terminal alkenes in high yields. The byproducts are easily removed, and the reaction conditions are mild and practical.

Acute kidney injury in a patient with nephrotic syndrome due to focal segmental glomerular nephritis induced by a single oral administration of high-dose bisphosphonate (minodronate).

We herein report the case of a 75-year-old man who developed an increased serum creatinine level (4.93 mg/dL) and oliguria with massive proteinuria (7.14 g/day) on the second day after a single oral administration of high-dose (56 mg) minodronate. The histology of a renal biopsy showed one area of glomerular sclerosis among 20 glomeruli with global foot process effacement of podocytes and mild infiltration of lymphocytes and eosinophils into the interstitial space. Acute kidney injury in nephrotic syndrome due to focal segmental glomerular sclerosis induced by minodronate was diagnosed. Following cessation of minodronate without the administration of immunosuppressive agents, the patient's renal function and proteinuria markedly improved.

Reversibility of structural and functional damage in a model of advanced diabetic nephropathy.

The reversibility of diabetic nephropathy remains controversial. Here, we tested whether replacing leptin could reverse the advanced diabetic nephropathy modeled by the leptin-deficient BTBR ob/ob mouse. Leptin replacement, but not inhibition of the renin-angiotensin-aldosterone system (RAAS), resulted in near-complete reversal of both structural (mesangial matrix expansion, mesangiolysis, basement membrane thickening, podocyte loss) and functional (proteinuria, accumulation of reactive oxygen species) measures of advanced diabetic nephropathy. Immunohistochemical labeling with the podocyte markers Wilms tumor 1 and p57 identified parietal epithelial cells as a possible source of regenerating podocytes. Thus, the leptin-deficient BTBR ob/ob mouse provides a model of advanced but reversible diabetic nephropathy for further study. These results also suggest that restoration of lost podocytes is possible but is not induced by RAAS inhibition, possibly explaining the limited efficacy of RAAS inhibitors in promoting repair of diabetic nephropathy.

Heart angiotensin II-induced cardiomyocyte hypertrophy suppresses coronary angiogenesis and progresses diabetic cardiomyopathy.

To examine whether and how heart ANG II influences the coordination between cardiomyocyte hypertrophy and coronary angiogenesis and contributes to the pathogenesis of diabetic cardiomyopathy, we used Spontaneously Diabetic Torii (SDT) rats treated without and with olmesartan medoxomil (an ANG II receptor blocker). In SDT rats, left ventricular (LV) ANG II, but not circulating ANG II, increased at 8 and 16 wk after diabetes onset. SDT rats developed LV hypertrophy and diastolic dysfunction at 8 wk, followed by LV systolic dysfunction at 16 wk, without hypertension. The SDT rat LV exhibited cardiomyocyte hypertrophy and increased hypoxia-inducible factor-1α expression at 8 wk and to a greater degree at 16 wk and interstitial fibrosis at 16 wk only. In SDT rats, coronary angiogenesis increased with enhanced capillary proliferation and upregulation of the angiogenic factor VEGF at 8 wk but decreased VEGF with enhanced capillary apoptosis and suppressed capillary proliferation despite the upregulation of VEGF at 16 wk. In SDT rats, the phosphorylation of VEGF receptor-2 increased at 8 wk alone, whereas the expression of the antiangiogenic factor thrombospondin-1 increased at 16 wk alone. All these events, except for hyperglycemia or blood pressure, were reversed by olmesartan medoxomil. These results suggest that LV ANG II in SDT rats at 8 and 16 wk induces cardiomyocyte hypertrophy without affecting hyperglycemia or blood pressure, which promotes and suppresses coronary angiogenesis, respectively, via VEGF and thrombospondin-1 produced from hypertrophied cardiomyocytes under chronic hypoxia. Thrombospondin-1 may play an important role in the progression of diabetic cardiomyopathy in this model.

Circumocular exanthema associated with chronic rejection after kidney transplantation.

A 43-year-old man had severe circumocular exanthema associated with chronic rejection 10 years after receiving a kidney transplant to treat end-stage renal failure. After the renal allograft was extracted, the exanthema diminished rapidly without any treatment. Donor-reactive immune cells seem to have cross-reacted with unknown pathogens on the skin and contributed to inflammation.

TGF-beta inhibits vascular sprouting through TGF-beta type I receptor in the mouse embryonic aorta.

Organogenesis accompanies the establishment of the vascular system which begins with sprouting angiogenesis. Vascular endothelial growth factor (VEGF) provides the primary stimulation in the vascular sprouting process but the negative regulation of this process remains unclear. This study examined the role of the transforming growth factor-beta (TGF-beta) superfamily in vascular sprouting using a three-dimensional dorsal aorta culture system, in which the dissected tissue was embedded in type I collagen gel. The cultures were maintained under hypoxic conditions to enhance the expression of Flk-1, a receptor for VEGF, thereby ensuring the responsibility to VEGF. Under the culture conditions employed, the dorsal aorta formed many cord-like structures in response to VEGF. To examine the role of TGF-beta in vascular sprouting, each member of the TGF-beta superfamily was applied to this culture system. TGF-beta1, as well as TGF-beta2 and TGF-beta 3, inhibited capillary formation. Likewise, activin A, another member of TGF-beta superfamily, also abolished vascular sprouting, but bone morphogenetic protein 2 did not noticeably change the morphology. Both neutralizing anti-TGF-beta1 antibody and TGF-beta type I receptor (ALK5) inhibitor partially reversed the inhibitory effect of TGF-beta1. Furthermore, down-regulation of ALK5 with small interfering RNA rather than activin receptor-like kinase-1 (ALK1) reversed the effect of TGF-beta1. These data suggest that TGF-beta superfamily may act as an inhibitor of vascular sprouting mainly through ALK5 signaling pathway. We propose that VEGF may antagonize the TGF-beta autoregulatory action to initiate vascular sprouting.

Transactivation of RON receptor tyrosine kinase by interaction with PDGF receptor beta during steady-state growth of human mesangial cells.

Although it is well known that platelet-derived growth factor (PDGF) causes mesangial cell proliferation (presumably contributing to progression of glomerular disease), targeted inhibition of the PDGF receptor system has shown only limited efficacy against glomerular diseases. To examine whether this discrepancy is due to the involvement of other pathways, we used phosphorylated receptor tyrosine kinase arrays and found that RON (recepteur d'origine nantais) was phosphorylated while the PDGF receptor was dephosphorylated (thus inactive) in human mesangial cells (HMCs) at the time of cell cycle entry. Further, RON remained active during steady-state growth. Activation of RON was independent of its canonical ligand, macrophage-stimulating protein, but was mediated by transactivation from the PDGF-engaged PDGF receptor. Following stimulation with PDGF we found that the two receptors physically interacted. Knockdown of RON by siRNA increased the number of apoptotic cells without affecting the rate of DNA synthesis, suggesting that RON has anti-apoptotic functions. Immunohistochemical analysis found phosphorylated RON in glomerular lesions of patients with IgA nephropathy but not those with minimal change nephrotic syndrome, a disease not associated with mesangial proliferation. These results suggest that RON is involved in mesangial cell proliferation under both physiological and pathological conditions, and may be a relevant target for therapeutic intervention.