Harald Seeger

Background: Wrist osteomyelitis caused by Scedosporium apiospermum is exceedingly rare. Its indolent course and destructive potential may result in extensive bone loss and pose substantial diagnostic and therapeutic challenges. Methods: We report a case of chronic wrist osteomyelitis caused by Scedosporium apiospermum in a 68-year-old kidney–pancreas transplant recipient. Results: Following diagnosis, systemic antifungal therapy with voriconazole was initiated, and multiple surgical debridements were performed to achieve local disease control, resulting in a large defect of the carpus and distal forearm. Hand salvage was attempted using an osteocutaneous triple-barrel fibula flap. The postoperative course was complicated by congestion of the fibula skin island, which was managed with leech therapy. Subsequent infection with a multi-resistant Aeromonas spp. and Morganella morganii led to flap necrosis, ultimately requiring transradial forearm amputation. Conclusions: Destructive Scedosporium apiospermum osteomyelitis in immunocompromised patients is a major challenge for reconstructive surgeons. Interdisciplinary management is essential as mold eradication is only achievable through a combined surgical and antimicrobial approach. In advanced destructive osteomyelitis, the choice between limb salvage and amputation should be individualized, considering patient comorbidities, reconstructive risk, and patients’ preferences. This case highlights the importance of balancing careful indication and patient counseling in complex clinical scenarios.

Background: Citrate is frequently applied in kidney stone formers (KSFs), yet long-term safety data are lacking. We evaluated the effects of prolonged citrate therapy on metabolic health, urinary risk factors and stone recurrence in high-risk KSFs in Switzerland. Methods: The Swiss Kidney Stone Cohort (SKSC) is a multicenter study including KSFs and controls. Blood and urine analyses were performed at baseline and longitudinally over 2 years in KSFs, with subsequent telephone follow-up for stone events. A total of 654 KSFs (110 with citrate, 544 without) and 207 controls were included. Outcomes comprised anthropometric indices (body mass index, body roundness index, waist-to-hip ratio), metabolic parameters, urinary relative supersaturation ratios (RSR), stone recurrence and stone composition. Results: No evidence for between-group differences in 1- to 2-year changes in anthropometric, glucose or lipid outcomes was identified. Anthropometric indices remained stable in both groups. HbA1c rose in non-citrate (NC) but not in citrate (C) group patients. High-density lipoprotein (HDL) cholesterol increased in both groups, while low-density lipoprotein (LDL) decreased only in C patients. Propensity score–matched analyses showed no between-group differences in 1- to 2-year changes in anthropometric, glucose or lipid outcomes, with only modest within-group changes in the C group (hemoglobin A1c, HDL- and LDL-cholesterol). Urine analyses showed a greater reduction in RSR for brushite among NC patients, whereas C patients had a stronger decline in uric acid (UA) RSR. Calcium oxalate RSR decreased similarly across groups. Stone recurrence was more frequent in C patients, with 43% versus 30% of NC patients changing stone type during follow-up. No shift toward calcium phosphate stones was observed in citrate users. Conclusions: Long-term citrate therapy appeared metabolically safe, and selectively reduced UA supersaturation, while non-treated patients showed a more pronounced decrease for brushite. Higher recurrence among treated patients may reflect different baseline risk. A prospective trial is warranted to clarify additive benefits of citrate beyond dietary-guided counseling.

BACKGROUND. Kidney stone disease (KSD) affects approximately 10% of the population. While genetic factors are known to play a role in KSD, determining the clinical relevance of rare variants in KSD genes identified in adults remains challenging. METHODS. The Swiss Kidney Stone Cohort is a multicenter longitudinal, observational study consisting of kidney stone formers (KSFs) (n = 701) and non-kidney stone formers (NKSFs) (n = 200). Blood and urine samples were collected at enrollment and over 3 years for deep biochemical phenotyping. Results were correlated with rare genetic variants in established KSD genes identified through whole-exome sequencing and classified according to American College of Medical Genetics and Genomics and the Association of Molecular Pathology (ACMG/AMP) criteria. RESULTS. Collectively, we found rare (likely) pathogenic (LP/P) variants representing strong KSD risk factors in 6.8% of KSFs, predominantly in genes involved in renal phosphate handling and cystinuria. Detailed biochemical analyses confirmed that KSFs carrying heterozygous LP/P SLC34A3 variants exhibited significant hyperphosphaturia. In contrast, monoallelic LP/P variants in SLC34A1, SLC9A3R1, or CYP24A1, which were also frequent in NKSFs, did not result in the expected biochemical alterations, calling into question their causative role as strong KSD risk factors. In cystinuria, monoallelic SLC7A9 variants represented intermediate risk factors, since they caused biochemical alterations but required additional factors for KSD occurrence, based on frequent LP/P variants in NKSFs. The presence of strong risk factors was associated with higher kidney stone (KS) recurrence over the 3-year observation period, supporting a predictive value for genetic testing. CONCLUSIONS. Correlation of genetic findings with thorough biochemical phenotyping and comparison with NKSFs redefines the clinical relevance of variants in KSD genes and has prognostic value.

Introduction: Increasing use of low-dose abdominal computed tomography (CT) scans in clinical diagnostics and research offers high sensitivity for kidney stones with minimal radiation exposure. However, due to reduced specificity, incidental findings potentially lead to unnecessary follow-up, financial burden, and psychological distress. Gaps of knowledge remain regarding the prevalence of incidental findings and their financial and psychological consequences. This study investigates the prevalence of incidental findings in asymptomatic participants undergoing low-dose non-contrast CT scans and their economic and psychological sequelae. Methods: We conducted a retrospective, multicentric observational study using data from the assessment for the control group of the Swiss Kidney Stone Cohort (SKSC). Low-dose non-contrast CT scans were analyzed for incidental findings, cost and psychological impact. Statistical analyses evaluated participant characteristics, financial and psychological consequences. Results: 229 participants underwent low-dose non-contrast CT scans, with 112 correctly completing the psychological questionnaires. The mean age was 42.9 years, and 56.3% were male. Incidental findings were observed in 47.2% (n = 108) of participants, with 16.6% having multiple findings. Kidney-related findings were the most prevalent, accounting for 35% of all findings. Of the incidental findings, 37.9% were classified as “incidentalomas” by the American College of Radiology (ACR) guidelines, and 15.7% of participants had findings that warranted follow-up according to radiology reports. In terms of costs, follow-up procedures, including imaging, consultations, and surgeries, incurred a total expense of 44’988 CHF, averaging 1967 CHF per participant and 2’999 CHF per incidental finding requiring follow-up. Surgical interventions were necessary for three participants, with individual costs reaching up to 35’208 CHF. Psychological assessment revealed that emotional distress and level of concern significantly differed across resilience levels and categories of CT findings. Participants with high resilience demonstrated lower emotional distress and concern, while those with CT findings requiring follow-up exhibited higher distress. Emotional distress was significantly greater in participants with follow-up findings compared to those without. Conclusions: Low-dose non-contrast abdominal CT scans often reveal incidental findings. Follow-up tests and procedures incurred significant financial costs, occasionally even leading to unnecessary surgical or non-surgical interventions. Psychological assessments showed increased anxiety in participants requiring follow-up, particularly those with low resilience. Our findings highlight the need for improved management, patient information, and consideration of economic and psychological impacts of incidental findings in clinical research and routine in the future.

Since the publication of the first Swiss recommendations on systemic light-chain amyloidosis in 2020, treatment strategies have evolved. As a result of the third joint meeting of the Swiss Amyloidosis Network, a multidisciplinary and multicentre Swiss clinical consortium, in 2024, recommendations for the treatment of light-chain amyloidosis were updated. They discuss the role of the new standard first-line protocol Daratumumab, Cyclophosphamide, Bortezomib, Dexamethasone (Dara-CyBorD), the timing and indication of high-dose treatment and potential second-line strategies as well as emerging treatment options, with a special focus on multidisciplinary supportive care measures. The update represents a synopsis of current evidence and expert consensus and intends to provide general treatment guidance tailored to the Swiss healthcare system. Nonetheless, treatment decisions should always be personalised and involve a multidisciplinary approach. This update replaces the previous “therapeutic recommendations” while the previous “diagnostic recommendations” remain valid.

Hepatitis E virus (HEV) infection, one of the most common forms of hepatitis worldwide, is often associated with extrahepatic, particularly renal, manifestations. However, the underlying mechanisms are incompletely understood. Here, we report the development of a de novo immune complex-mediated glomerulonephritis (GN) in a kidney transplant recipient with chronic hepatitis E. Applying immunostaining, electron microscopy, and mass spectrometry after laser-capture microdissection, we show that GN develops in parallel with increasing glomerular deposition of a non-infectious, genome-free and non-glycosylated HEV open reading frame 2 (ORF2) capsid protein. No productive HEV infection of kidney cells is detected. Patients with acute hepatitis E display similar but less pronounced deposits. Our results establish a link between the production of HEV ORF2 protein and the development of hepatitis E-associated GN in the immunocompromised state. The formation of glomerular IgG-HEV ORF2 immune complexes discovered here provides a potential mechanistic explanation of how the hepatotropic HEV can cause variable renal manifestations. These findings directly provide a tool for etiology-based diagnosis of hepatitis E-associated GN as a distinct entity and suggest therapeutic implications.

Hyperparathyroidism (HPT) with hypercalcemia, often deemed irreversible and detrimental to graft survival post-kidney transplantation (KT), prompts pre-transplant parathyroidectomy in hypercalcemic patients. In this retrospective analysis of 1212 kidney transplant recipients (KTRs) between 2006 and 2019, the incidence and effect of persistent HPT and hypercalcemia on graft and patient survival, and risk factors for persistence were analyzed until 60 months of follow up (FU). At KT, 5.7% (n = 69) had no HPT, 32.7% (n = 396) had HPT without hypercalcemia and 37.0% (n = 448) had HPT with hypercalcemia. At 2 years FU, 26.4% (n = 320) of patients had no HPT and 6% (n = 73) had HPT with hypercalcemia. Dialysis and dialysis duration were linked to HPT development, while dialysis, KT waiting time and donor type correlated with persisting hypercalcemia after KT. KTRs with normalized PTH and recovered hypercalcemia had improved death-censored graft survival (p < 0.001) and overall patient survival (p < 0.001). HPT with hypercalcemia is frequent at time of KT with normalization of PTH and calcium in a substantial proportion of patients after a KT. These findings question the routine pre-KT parathyroidectomy for suspected parathyroid autonomy. Persisting HPT, especially with hypercalcemia, adversely affects graft and patient survival, suggesting the need for more aggressive treatment of HPT, especially in cases of persisting hypercalcemia.

Background: Kidney stones are frequent in industrialized countries with a lifetime risk of 10 to 15%. A high percentage of individuals experience recurrence. Calcium-containing stones account for more than 80% of kidney stones. Diet, environmental factors, behavior, and genetic variants contribute to the development of kidney stones. Osteocytes excrete the 21 kDa glycoprotein sclerostin, which inhibits bone formation by osteoblasts. Animal data suggests that sclerostin might directly or indirectly regulate calcium excretion via the kidney. As hypercalciuria is one of the most relevant risk factors for kidney stones, sclerostin might possess pathogenic relevance in nephrolithiasis. Methods: We performed a prospective cross-sectional observational controlled study in 150 recurrent kidney stone formers (rKSF) to analyse the association of sclerostin with known stone risk factors and important modulators of calcium-phosphate metabolism. Serum sclerostin levels were determined at the first visit. As controls, we used 388 non-stone formers from a large Swiss epidemiological cohort. Results: Sclerostin was mildly increased in rKSF in comparison to controls. This finding was more pronounced in women compared to men. Logistic regression indicated an association of serum sclerostin with rKSF status. In hypercalciuric individuals, sclerostin levels were not different from normocalciuric patients. In Spearman correlation analysis we found a positive correlation between sclerostin, age, and BMI and a negative correlation with eGFR. There was a weak correlation with iPTH and intact FGF 23. In contrast, serum sclerostin levels were not associated with 25-OH Vitamin D3, 1,25-dihydroxy-Vitamin D3, urinary calcium and phosphate or other urinary lithogenic risk factors. Conclusion: This is the first prospective controlled study investigating serum sclerostin in rKSF. Sclerostin levels were increased in rKSF independent of hypercalciuria and significantly associated with the status as rKSF. It appears that mechanisms other than hypercalciuria may be involved and thus further studies are required to elucidate underlying pathways.